Search

Background: The incidental use of statins during radiation therapy has been associated with a reduced long-term risk of developing atherosclerotic cardiovascular disease. We examined whether irradiation causes chronic vascular injury and whether short-term administration of statins during and after irradiation is sufficient to prevent chronic injury compared with long-term administration., Methods and Results: C57Bl/6 mice were pretreated with pravastatin for 72 hours and then exposed to 12 Gy X-ray head-and-neck irradiation. Pravastatin was then administered either for an additional 24 hours or for 1 year. Carotid arteries were tested for vascular reactivity, altered gene expression, and collagen deposition 1 year after irradiation. Treatment with pravastatin for 24 hours after irradiation reduced the loss of endothelium-dependent vasorelaxation and protected against enhanced vasoconstriction. Expression of markers associated with inflammation (NFκB p65 [phospho-nuclear factor kappa B p65] and TNF-α [tumor necrosis factor alpha]) and with oxidative stress (NADPH oxidases 2 and 4) were lowered and subunits of the voltage and Ca 2+ activated K + BK channel (potassium calcium-activated channel subfamily M alpha 1 and potassium calcium-activated channel subfamily M regulatory beta subunit 1) in the carotid artery were modulated. Treatment with pravastatin for 1 year after irradiation completely reversed irradiation-induced changes., Conclusions: Short-term administration of pravastatin is sufficient to reduce chronic vascular injury at 1 year after irradiation. Long-term administration eliminates the effects of irradiation. These findings suggest that a prospective treatment strategy involving statins could be effective in patients undergoing radiation therapy. The optimal duration of treatment in humans has yet to be determined.

Pulsed dye lasers are used effectively in the treatment of psoriasis with long remission time and limited side effects. It is, however, not completely understood which biological processes underlie its favorable outcome. Pulsed dye laser treatment at 585-595 nm targets hemoglobin in the blood, inducing local hyperthermia in surrounding blood vessels and adjacent tissues. While the impact of destructive temperatures on blood vessels has been well studied, the effects of lower temperatures on the function of several cell types within the blood vessel wall and its periphery are not known. The aim of our study is to assess the functionality of isolated blood vessels after exposure to moderate hyperthermia (45 to 60°C) by evaluating the function of endothelial cells, smooth muscle cells, and vascular nerves. We measured blood vessel functionality of rat mesenteric arteries (n=19) by measuring vascular contraction and relaxation before and after heating vessels in a wire myograph. To this end, we elicited vascular contraction by addition of either high potassium solution or the thromboxane analogue U46619 to stimulate smooth muscle cells, and electrical field stimulation (EFS) to stimulate nerves. For measurement of endothelium-dependent relaxation, we used methacholine. Each vessel was exposed to one temperature in the range of 45-60°C for 30 seconds and a relative change in functional response after hyperthermia was determined by comparison with the response per stimulus before heating. Non-linear regression was used to fit our dataset to obtain the temperature needed to reduce blood vessel function by 50% (Half maximal effective temperature, ET50). Our findings demonstrate a substantial decrease in relative functional response for all three cell types following exposure to 55°C-60°C. There was no significant difference between the ET50 values of the different cell types, which was between 55.9°C and 56.9°C (P>0.05). Our data show that blood vessel functionality decreases significantly when exposed to temperatures between 55°C-60°C for 30 seconds. The results show functionality of endothelial cells, smooth muscle cells, and vascular nerves is similarly impaired. These results help to understand the biological effects of hyperthermia and may aid in tailoring laser and light strategies for selective photothermolysis that contribute to disease modification of psoriasis after pulsed dye laser treatment., (© 2024. The Author(s).)

Dental resin curing blue light (BL) is frequently used during treatments in dental clinics. However, little is known about the influence of BL irradiation on pulpal blood vessels. The aim of the present study was to investigate the mechanism of effect of BL irradiation on vascular tone. Rat aorta (RA) rings were irradiated with a BL source in organ baths, and the responses were recorded isometrically. Effect of BL irradiation on phenylephrine (PE) -precontraction and acetylcholine (ACh) -induced relaxation after PE -precontraction were obtained and compared in BL -irradiated and control RA rings. Effect of 20 min preincubation with catalase (enzyme that breaks down hydrogene peroxide, 1200 u/ml) on PE -precontraced and BL-irradiated rings was also evaluated. Total oxidative stress (TOS) and total antioxidant capacity (TAC) in BL-irradiated and control RA preparations were measured with special assay kits and spectrophotometry. BL slightly decreased ACh -induced endothelium -dependent relaxations in PE (1 μM) -precontracted RA rings (n = 6, p > 0.05 vs. control). BL induced marked contraction 23.88 + 3.10% of PE (maximum contraction) in isolated RA ring segments precontracted with PE (p < 0.05 vs. control). The contractile effect of BL was inhibited by 1200 u/ml catalase (n = 6, p < 0.05 vs. control). BL irradiation increased the level of TOS in RA rings (n = 6, p < 0.05 vs. control). TAC levels were similar in BL-irradiated and control preparations. These results suggest that BL induces contraction in RA, and the mechanism of this effect may to be through release of hydrogen peroxide., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Objective: Port wine stains (PWS) are congenital vascular malformations that progressively darken and thicken with age. Laser therapy is currently the most effective way in clinical practice for PWS. A 1,064 nm Nd:YAG laser in the near-infrared band can achieve a deeper treatment depth compared to the current widely adopted pulsed dye laser. However, because of its relatively weak absorption by blood, single-pulse Nd:YAG laser requires high energy density to cause effective vessel damage, but may inflict undesirable burning to surrounding collagen. Multi-pulse laser has great potential in clinical treatment because it needs less energy density for each pulse. This paper presented an experimental and theoretical study of the transient thermal effects of low-energy multi-pulse Nd:YAG laser on blood vessels., Study Design/materials and Methods: In vivo experiments were performed on dorsal skin chamber. By using a high speed camera (up to 2,000 fps), the complete and dynamic thermal response of blood vessels during laser irradiation and between pulse intervals was obtained. In vitro experiment in capillary tubes and Numerical simulations by two-scale heat transfer model were also conducted to further explore the in vivo experimental findings., Results: The complete and dynamic response of blood vessels were obtained, including vessel dilation, thrombus formation, partial vessel constriction, thread-like constriction, cavitation and bubbles, and hemorrhage. Thread-like constriction is the desirable treatment end point, which will only occur after thrombus completely occludes the vessel lumen. Cavitation can cause hemorrhage when thrombus fails to occlude the vessel lumen. In vitro experiment found that vessel constriction was due to the constriction of thrombus induced by laser irradiation. Theoretical investigation revealed that the mechanism for the effective reduction of energy density by multi-pulse Nd:YAG laser was due to enhanced light absorption of the blood with thrombus formation., Conclusions: For multi-pulse treatment, laser parameters are recommended as repetition rate of 10 Hz and pulse number of 10. The incident energy in each pulse should be strong enough to induce blood coagulation through seven or eight pulses and should be lower than the threshold of blood cavitation. Lasers Surg. Med. 49:852-865, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

This study investigated thermal changes in the skin at locations where soft tissue defects existed and acupuncture needles stimulated by using bipolar electroacupuncture (EA) had been inserted. Under general anesthesia (GA), experimental defects were made at the dorsum site of five New Zealand rabbits. Bipolar EA was used for 20 minutes to stimulate the experimental defects, and the skin temperature was monitored at the sites where the acupuncture needles had been inserted and the soft tissue defects existed. The initial thermography of those defects had the same trend as that of the negative pole of EA stimulation at the first acupoint. Skin thermography during the first 3 minutes of bipolar EA indicated a centrifugal vasoconstriction and a vasodilatation at the negative and positive poles, respectively. After that, the thermal change in soft tissue undergoing EA stimulation was not modified by a different EA polarity. The local temperature at the defect and its surroundings under both positive and negative electric loads was increased by 0.2-0.3 °C for vasodilatation. This study indicates that EA influences sympathetic modulation of soft tissue defects and that selective sympathetic modulation caused by bipolar EA is responsible for the clinical perception., (Copyright © 2014. Published by Elsevier B.V.)

Noncompressible hemorrhage is currently the most common cause of preventable death in battlefield and in civilian trauma injuries. Tourniquets, specialized wound dressings, and hemorrhage-inhibiting biomaterials are not sufficiently effective in arrest of noncompressible hemorrhage and often cause collateral tissue damage. An effective, easy-to-use, portable device is needed to reduce blood loss in trauma patients immediately following injury and to maintain hemorrhage control up to several hours-until the injured is evacuated to a medical facility. We developed a miniature electrical stimulator to induce vascular constriction and, thereby, reduce hemorrhage. Vasoconstriction of the rat femoral arteries and veins was studied with pulse durations in the range of 1 μs to 10 ms and repetition rate of 10 Hz. Pulse amplitude of 20 V, duration of 1 ms, and repetition rate of 10 Hz were found sufficient to induce rapid constriction down to 31 ± 2% of the initial diameter, which could be maintained throughout a two-hour treatment. Within one minute following treatment termination the artery dilated back to 88 ± 3% of the initial diameter, providing rapid restoration of blood perfusion. Histology indicated no damage to the vessel wall and endothelium seven days after stimulation. The same treatment reduced the blood loss following complete femoral artery resection by 68 ± 11%, compared to untreated vessels. Very low power consumption during stimulation (<10 mW per 1.6 mm electrode) allows miniaturization of the stimulator for portable battery-powered operation in the field to control the blood loss following vascular trauma.

Background: In a previous study it is shown that for topically applied ALA-PDT, PpIX concentration correlates with vascular changes including vasoconstriction and/or vascular leakage of small vessels and arterioles in the mouse epidermis and dermis. In this study we report on vascular responses induced by ALA-PDT for different fluence rates, including both changes in vessel diameter and dynamics in RBC velocity in arterioles, imaged using intra-vital confocal microscopy in skinfold chambers in hairless mice. Our interest is in the dynamics of vascular changes in the early stages of illumination., Methods: We have determined the total PDT dose to be relatively low, 13 J cm(-2), and fluence rates of 26, 65 and 130 mW cm(-2) were investigated. Local vascular effects occurred very soon after the start of the therapeutic illumination in ALA-PDT., Results: In this study, we did not find a significant difference between fluence rates. Arterioles were particularly sensitive to vasoconstriction during low dose PDT, often resulting in complete vasoconstriction. When we observed complete vasoconstriction, this coincided with changes in RBC velocity., Conclusion: Since the therapeutic effects of PDT are dependent on a fine balance between the need for oxygen during illumination and disruption of the vasculature, the results of the present study add to our understanding of acute vascular effects during ALA-PDT and aid our efforts to optimize PDT using porphyrin pre-cursors., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Chronic kidney disease (CKD) is regarded as a state of Klotho deficiency and FGF23 excess. In patients with CKD a strong association has been found between increased serum FGF23 and mortality risk, possibly via enhanced atherosclerosis, vascular stiffness, and vascular calcification. The aim of this study was to examine the hypothesis that soluble Klotho and FGF23 exert direct, rapid effects on the vessel wall. We used three in vitro models: mouse aorta rings, human umbilical vein endothelial cells, and human vascular smooth muscle cells (HVSMC). Increasing medium concentrations of soluble Klotho and FGF23 both stimulated aorta contractions and increased ROS production in HVSMC. Klotho partially reverted FGF23 induced vasoconstriction, induced relaxation on phosphate preconstricted aorta and enhanced endothelial NO production in HUVEC. Thus Klotho increased both ROS production in HVSMC and NO production in endothelium. FGF23 induced contraction in phosphate preconstricted vessels and increased ROS production. Phosphate, Klotho and FGF23 together induced no change in vascular tone despite increased ROS production. Moreover, the three compounds combined inhibited relaxation despite increased NO production, probably owing to the concomitant increase in ROS production. In conclusion, although phosphate, soluble Klotho and FGF23 separately stimulate aorta contraction, Klotho mitigates the effects of phosphate and FGF23 on contractility via increased NO production, thereby protecting the vessel to some extent against potentially noxious effects of high phosphate or FGF23 concentrations. This novel observation is in line with the theory that Klotho deficiency is deleterious whereas Klotho sufficiency is protective against the negative effects of phosphate and FGF23 which are additive.

Vascular responses to photodynamic therapy (PDT) may influence the availability of oxygen during PDT and the extent of tumor destruction after PDT. However, for topical PDT vascular effects are largely unknown. Arteriole and venule diameters were measured before and after hexylaminolevulinate (HAL) and aminolevulinic acid (ALA) PDT and related to the protoporphyrin IX (PpIX) concentration in the vessel wall. A mouse skin fold chamber model and an intravital confocal microscope allowed direct imaging of the subcutaneous vessels underlying the treated area. In both HAL and ALA groups over 60% of arterioles constricted completely, while venules generally did not respond, except for two larger veins that constricted partially. Arteriole vasoconstriction strongly correlated with PpIX fluorescence intensity in the arteriole wall. Total PpIX fluorescence intensity was significantly higher for HAL than ALA for the whole area that was imaged but not for the arteriole walls. In conclusion, complete arteriole vasoconstriction occurs frequently in both HAL and ALA based topical PDT, especially when relatively high PpIX concentrations in arteriole walls are reached. Vasoconstriction will likely influence PDT effect and should be considered in studies on topical HAL and ALA-PDT. Also, our results may redefine the vasculature as a potential secondary target for topical PDT., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The effects of radiofrequency electromagnetic fields (RF-EMF) on the control of body energy balance in developing organisms have not been studied, despite the involvement of energy status in vital physiological functions. We examined the effects of chronic RF-EMF exposure (900 MHz, 1 V m(-1)) on the main functions involved in body energy homeostasis (feeding behaviour, sleep and thermoregulatory processes). Thirteen juvenile male Wistar rats were exposed to continuous RF-EMF for 5 weeks at 24 °C of air temperature (T a) and compared with 11 non-exposed animals. Hence, at the beginning of the 6th week of exposure, the functions were recorded at T a of 24 °C and then at 31 °C. We showed that the frequency of rapid eye movement sleep episodes was greater in the RF-EMF-exposed group, independently of T a (+42.1 % at 24 °C and +31.6 % at 31 °C). The other effects of RF-EMF exposure on several sleep parameters were dependent on T a. At 31 °C, RF-EMF-exposed animals had a significantly lower subcutaneous tail temperature (-1.21 °C) than controls at all sleep stages; this suggested peripheral vasoconstriction, which was confirmed in an experiment with the vasodilatator prazosin. Exposure to RF-EMF also increased daytime food intake (+0.22 g h(-1)). Most of the observed effects of RF-EMF exposure were dependent on T a. Exposure to RF-EMF appears to modify the functioning of vasomotor tone by acting peripherally through α-adrenoceptors. The elicited vasoconstriction may restrict body cooling, whereas energy intake increases. Our results show that RF-EMF exposure can induce energy-saving processes without strongly disturbing the overall sleep pattern.

Background and Objective: As low-level laser irradiation (LLLI) seems to induce vasodilation besides many other known biological effects, LLLI has been increasingly used in therapy of medical conditions with various irradiation parameters. The aim of this study was to investigate the effect of LLLI on photorelaxation of human coronary and internal thoracic arteries (ITA)., Materials and Methods: Thirty vessel segments of ITA used for routine coronary artery bypass grafting as well as left anterior descending coronary arteries (LAD) of patients undergoing cardiac transplantation were cut into 4-mm rings stored in a modified Krebs-Henseleit solution and evaluated in a myograph. Both types of vessel segments were irradiated by a semiconductor non-thermal GaAs diode laser operating at a wavelength of 680 nm. After precontraction with thromboxane agonist U44619, respective relaxation responses were evaluated and compared to pharmacological dilatation induced by substance P., Results: Mean pharmacological vasodilation by substance P was 22.6 ± 3.3%, 12.8 ± 1.4%, and 20.4 ± 3.2% in macroscopic healthy LAD, LAD with atheromatous plaque, and ITA, respectively. Average photorelaxation induced by LLLI was 16.5 ± 2.0%, 1.9 ± 1.7%, and 6.8 ± 4.7%, accordingly. Vasodilatatory responses induced either by substance P or administration of LLLI were significantly decreased in LAD with atheromatous plaque (P < 0.0001). Vasospasms of ITA segments occurring during experiments could be abandoned when LLLI was administered., Conclusion: Macroscopic healthy LAD exposed to LLLI revealed significant photorelaxation. With the administration of LLLI, 73% of the maximal obtainable effect by an endothelium-dependent vasodilator could be reached. Furthermore, LLLI has the potential to overcome vasospasms of ITA., (Copyright © 2012 Wiley Periodicals, Inc.)

This review covers the molecular-cellular mechanisms of therapeutic action of light and magnetic field on blood components, blood vessels and the microcirculation system. Noted the role of the magnetic field as a trigger of vasodilation/vasoconstriction, depending on the initial vascular tone. Discussed the importance of NO-dependent effects of magnetic field on the microcirculatory response and angiogenesis.

We have previously shown that MHz frequency ultrasound causes contraction of the carotid artery in vitro. We now extend this investigation to equine mesenteric arteries and investigate the cellular mechanisms. In vitro exposure of the large lateral cecal mesenteric artery to 4-min periods of 3.2 MHz continuous wave ultrasound at acoustic powers up to 145 mW induced reversible repeatable contraction. The magnitude of the response was linearly dependent on acoustic power and, at 145 mW, the mean increase in wall stress was 0.020 ± 0.017 mN/mm(2) (n = 34). These results are consistent with our previous study and the effect was hypothesised to be thermally mediated. A 2°C temperature rise produced an increase in intracellular calcium, measured by Fluo-4 fluorescence. Inhibition of the inward-rectifier potassium ion channel with BaCl(2) (4 μM) increased the response to ultrasound by 55% ± 49%, indicating a similar electrophysiologic basis to the response to mild hyperthermia. In small mesenteric arteries (0.5-1.0 mm diameter) mounted in a perfusion myograph, neither ultrasound exposure nor heating produced measureable vasoconstriction or a rise in intracellular calcium and we conclude that temperature-sensitive channels are absent or inactive in these small vessels. It, therefore, appears that response of blood vessels to ultrasound depends not only on the thermal properties of the vessels and surrounding tissues but also on the electrophysiology of the smooth muscle cells., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: Retinal vessel responses to flickering light are different in various systemic and ocular diseases and can be improved after successful therapy. We investigated retinal vessel response to flickering light in age-related macular degeneration (AMD) patients before and after treatment with a single intravitreal bevacizumab (Avastin(®) ) injection., Methods: In 10 patients with exudative AMD [age: median (1.quartile; 3.quartile) 76.0 (73.5; 80.0) years], retinal vessel reactions were examined by Dynamic Vessel Analyser (DVA) before and 3 months after a single intravitreal application of bevacizumab (1.25 mg). A baseline measurement was followed by three consecutive monochromatic flicker stimulations (530-600 nm, 12.5 Hz, 20 seconds). Temporal retinal vessel reaction was analysed and compared with the reaction in healthy controls., Results: Mean arterial dilation at the end of flicker was not different in all groups. For veins this parameter amounted to: pre-treatment, 2.6 (1.7; 3.9)%; post-treatment, 2.9 (2.4; 4.0)%; control, 4.3 (3.2; 5.7)%; significant: pre-treatment - control (Dunnett's procedure, p < 0.05). Maximal dilation occurred in arteries at: pre-treatment, 17.5 (14.8; 32.5) seconds; post-treatment, 18.0 (16.6; 30.6) seconds; control, 14.5 (10.8; 17.3) seconds. Both AMD groups were slower (p < 0.05): in veins at 17.0 (14.5; 20.0) seconds, 12.8 (8.6; 14.8) seconds and 18.5 (17.1; 19.9) seconds, respectively; significant post-treatment - control (p < 0.05). In the post-treatment AMD group arterial constriction after stimulation occurred more slowly compared with the control group (p < 0.05)., Conclusion: Dynamic retinal arterial and venous reactions to flickering light are altered in AMD compared with controls. Three months after a single injection of a vascular endothelial growth factor inhibitor, the investigated retinal dynamic vascular parameters were not altered in our study., (© 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.)

Background: The purpose of this study is to elucidate if there is an additive or supra-additive toxic effects of radiotherapy (RT) and trastuzumab (T) on vascular structures when used concomitantly., Methods: Female Wistar albino rats were treated with either 8 or 15 Gy of thoracic RT. T was applied i.p. with a dose of 6 mg/kg 2 h before RT. Four rats in each arm were killed at 6th h, 21st and 70th days after irradiation and thoracic aorta of each animal was dissected for electron microscopy. In addition, functional studies for evaluating the relaxation and contraction were carried out 21 days after RT., Results: Only 15-Gy RT dose groups showed significant difference in terms of functional deterioration as more contraction than the others (P < 0.05) without any difference between RT and RT + T. However, T produced additional deficit in relaxation when added to RT, which was considered near significant (P: 0.0502). Electron microscopy showed endothelial and subendotelial damage signs in 15-Gy dose groups. T + 15-Gy arm showed more pronounced endothelial cell damage than 15-Gy RT-only arm, 70 days after RT., Conclusion: T and high-dose RT may lead to vascular damage that seems at least additive.

Experiments on WKY and SHR rats showed that low-intensity laser irradiation reduced the tone of pial arterial vessels thereby potentiating the subsequent constrictor effect of norepinephrine. Irradiation in the red region of the spectrum produced a more pronounced effect in the blue region. The observed effects were less pronounced in SHR rats compared to normotensive WKY rats.

Background: Antiangiogenic and anti-vascular therapies present intriguing alternatives to cancer therapy. However, despite promising preclinical results and significant delays in tumor progression, none have demonstrated long-term curative features to date. Here, we show that a single treatment session of Tookad-based vascular targeted photodynamic therapy (VTP) promotes permanent arrest of tumor blood supply by rapid occlusion of the tumor feeding arteries (FA) and draining veins (DV), leading to tumor necrosis and eradication within 24-48 h., Methodology/principal Findings: A mouse earlobe MADB106 tumor model was subjected to Tookad-VTP and monitored by three complementary, non-invasive online imaging techniques: Fluorescent intravital microscopy, Dynamic Light Scattering Imaging and photosensitized MRI. Tookad-VTP led to prompt tumor FA vasodilatation (a mean volume increase of 70%) with a transient increase (60%) in blood-flow rate. Rapid vasoconstriction, simultaneous blood clotting, vessel permeabilization and a sharp decline in the flow rates then followed, culminating in FA occlusion at 63.2 sec+/-1.5SEM. This blockage was deemed irreversible after 10 minutes of VTP treatment. A decrease in DV blood flow was demonstrated, with a slight lag from FA response, accompanied by frequent changes in flow direction before reaching a complete standstill. In contrast, neighboring, healthy tissue vessels of similar sizes remained intact and functional after Tookad-VTP., Conclusion/significance: Tookad-VTP selectively targets the tumor feeding and draining vessels. To the best of our knowledge, this is the first mono-therapeutic modality that primarily aims at the larger tumor vessels and leads to high cure rates, both in the preclinical and clinical arenas.

Purpose: To find the mitigators of pneumonitis induced by moderate doses of thoracic radiation (10-15 Gy)., Methods and Materials: Unanesthetized WAG/RijCmcr female rats received a single dose of X-irradiation (10, 12, or 15 Gy at 1.615 Gy/min) to the thorax. Captopril (an angiotensin-converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in the drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating the breathing rate, ex vivo vascular reactivity, and histopathologic findings. Survival analysis was undertaken on all animals, except those scheduled for death., Results: Survival after a dose of 10 Gy to the thorax was not different from that of unirradiated rats for

A variety of medical procedures is aimed to selectively compromise or destroy vascular function. Such procedures include cancer therapies, treatments of cutaneous vascular disorders, and temporary hemostasis during surgery. Currently, technologies such as lasers, cryosurgery and radio frequency coagulation, produce significant collateral damage due to the thermal nature of these interactions and corresponding heat exchange with surrounding tissues. We describe a non-thermal method of inducing temporary vasoconstriction and permanent thrombosis using short pulse (microseconds) electrical stimulation. The current density required for vasoconstriction increases with decreasing pulse duration approximately as t(-0.25). The threshold of electroporation has a steeper dependence on pulse duration-exceeding t(-0.5). At pulse durations shorter than 5 micros, damage threshold exceeds the vasoconstriction threshold, thus allowing for temporary hemostasis without direct damage to surrounding tissue. With a pulse repetition rate of 0.1 Hz, vasoconstriction is achieved approximately 1 min after the beginning of treatment in both arteries and veins. Thrombosis occurs at higher electric fields, and its threshold increases with vessel diameter. Histology demonstrated a lack of tissue damage during vasoconstriction, but vascular endothelium was damaged during thrombosis. The temperature increase does not exceed 0.1 degrees C during these treatments., ((c) 2007 Wiley-Liss, Inc.)

Exposure of the skin to ultraviolet A (UVA) results in various biological responses, skin-colour changes being among the major ones. Although intense research has been performed on UVA-induced pigmentation and vascular changes, the process of skin-colour changes after UVA irradiation remains unclear. For a better understanding of the UVA tanning mechanism, we here performed a human study in 27 healthy volunteers with skin phototype (SPT) II to VI. After a single UVA exposure to inner forearm, the skin sites were imaged using reflectance-mode confocal microscopy (RCM), for analysis of melanin and vascular changes. Punch biopsies were also taken from the UVA-exposed or non-exposed sites for histological examination. Skin sections were stained with Fontana-Masson and evaluated by a sensitive tyrosinase assay for comparison with RCM images. Furthermore, the effect of blood flow on skin-colour changes was evaluated visually after administration of an intradermal anesthesia of lidocaine with or without epinephrine. Our RCM analysis showed dendritic melanocytes and a different melanin distribution in the epidermal layer, clearly visible 1 week after the UVA exposure in subjects of SPT V which were supported by histological examination. However, no melanin distribution pattern changes were apparent immediately after the exposure, while RCM images showed accelerated capillary flow patterns. The restriction of this UVA induced-accelerated blood flow by epinephrine inhibited partially or completely the immediate pigment darkening and delayed tanning. These in vivo studies confirmed that vascular change is an important factor for the development of the immediate pigment darkening and delayed tanning.

Photoactivable caged analogs of endothelin-1 (ET-1) were obtained after derivatization with the photolabile 4,5-dimethoxynitrobenzyl (DMNB) group. This was achieved by the incorporation of N-alpha-Fmoc caged building blocks of Lys, Asp, Glu and Tyr during the solid phase peptide synthesis step. The C-terminal carboxylic function was also derivatized. However, difficulties were encountered with the introduction of the Asp and Glu photoactivable building blocks. As a matter of fact, formation of an aminosuccinyl derivative, through cyclization of the Asp(ODMNB) residue, and the formation of a pyrrolidone ring from the Glu(ODMNB) residue were highly favored by the electronic properties of the photocleavable function. ET-1 analogs were also tested in the ET(A) and ET(B) paradigms and specific pharmacological profiles were obtained for each peptide.

Purpose: To determine whether clinically relevant doses of sodium fluorescein produce changes in vascular tone in retinal arterioles and veins and whether any such effects were light dependent., Methods: Segments of porcine retinal arterioles and veins were dissected, cannulated, and perfused and their outer diameter monitored during intraluminal application of increasing doses (10(-10) to 10 (-3) g/ml) of sodium fluorescein under either brightly lit (350 lux) or dimly lit (4 lux) conditions. The significance of any induced change in vessel diameter was assessed in relation to the initial vessel diameter., Results: At the higher light level, sodium fluorescein produced a significant dose-dependent contraction in porcine retinal arterioles and veins with a threshold of 10 (-5) g/ml and 10 (-9) g/ml sodium fluorescein, respectively. At the maximal dose tested (10(-3) g/ml), vessel diameter was reduced to approximately 85% of the initial vessel diameter in retinal arterioles and veins. Under dimly lit conditions, the vasoconstrictive effect of sodium fluorescein was still evident but the constriction was significantly smaller (p < 0.05) in both arteries and veins, reaching approximately 91% and 93%, respectively., Conclusions: Sodium fluorescein induced light-dependent vasoconstrictive effects on the retinal vasculature of the pig. Should a similar effect be present in human retinal vessels, then reduced illumination level may limit the vasoconstrictive effects of sodium fluorescein when used in routine ophthalmic examinations.

Purpose: The generation of reactive oxygen species during gamma-irradiation may induce DNA damage, leading to activation of the nuclear enzyme poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) culminating in endothelial dysfunction. In the present study, we assessed the effect of PARP inhibition on changes in vascular function after acute and short-term irradiation., Methods and Materials: In the acute experiments, aortic rings were exposed to 20 Gy of gamma-irradiation. The aortae were harvested after 1 or 7 days. Two additional groups received the ultrapotent PARP inhibitor, INO-1001, for 1 or 7 days after irradiation. The aortic rings were precontracted by phenylephrine and relaxation to acetylcholine and sodium nitroprusside were studied., Results: The vasoconstrictor response to phenylephrine was significantly lower both acutely and 1 and 7 days after irradiation. Vasorelaxation to acetylcholine and sodium nitroprusside was not impaired acutely after irradiation. One and seven days after irradiation, vasorelaxation to acetylcholine and sodium nitroprusside was significantly enhanced. Treatment with INO-1001 reversed vascular dysfunction after irradiation., Conclusion: Vascular dysfunction was observed 1 and 7 days after irradiation, as evidenced by reduced vasoconstriction, coupled with endothelium-dependent and -independent hyperrelaxation. PARP inhibition restored vascular function and may, therefore, be suitable to reverse vascular dysfunction after irradiation.

Background: Light exposure of TPN generates peroxides which induce vasoconstriction. Mesenteric vasoconstriction may affect feeding tolerance. Since photo-protection of TPN decreases peroxide generation, we hypothesized that shielding TPN from light may improve the establishment of minimal enteral nutrition in preterm infants., Methods: Infants were randomized to TPN being light exposed (LE) or protected (LP) from birth. Feeding volumes were monitored through 7 days of life in those initiated on minimal enteral nutrition (MEN). Comparisons between LP and LE were performed by ANOVA., Results: Daily increments and cumulative volumes of enteral feeds (mL/kg birth weight/d) during the first week of life were significantly higher in LP (n = 18) than LE (n = 19)., Conclusion: Photo-protection of parenteral nutrition enhances advancement of MEN in preterm infants. Further research is needed to substantiate these findings and determine whether this confers long-term nutritional advantages.

Neuronal activity evokes localized changes in blood flow. Although this response, termed neurovascular coupling, is widely used to monitor human brain function and diagnose pathology, the cellular mechanisms that mediate the response remain unclear. We investigated the contribution of glial cells to neurovascular coupling in the acutely isolated mammalian retina. We found that light stimulation and glial cell stimulation can both evoke dilation or constriction of arterioles. Light-evoked and glial-evoked vasodilations were blocked by inhibitors of cytochrome P450 epoxygenase, the synthetic enzyme for epoxyeicosatrienoic acids. Vasoconstrictions, in contrast, were blocked by an inhibitor of omega-hydroxylase, which synthesizes 20-hydroxyeicosatetraenoic acid. Nitric oxide influenced whether vasodilations or vasoconstrictions were produced in response to light and glial stimulation. Light-evoked vasoactivity was blocked when neuron-to-glia signaling was interrupted by a purinergic antagonist. These results indicate that glial cells contribute to neurovascular coupling and suggest that regulation of blood flow may involve both vasodilating and vasoconstricting components.

In both conscious and anesthetized rabbits, we determined whether microinjection of a 5-hydroxytryptamine (5-HT) 1A receptor agonist 8-hydroxy-2-(di-n-propylaminio) tetralin (8-OH-DPAT) into the medullary raphé/parapyramidal region inhibits thermoregulatory vasoconstriction and whether microinjection of a 5-HT1A receptor antagonist (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2-pyridinyl) cyclohexanecarboxamide trihydrochloride) (WAY-100635) into the raphé reverses the cutaneous vasomotor changes induced by intravenous administration of 8-OH-DPAT. In conscious rabbits with measuring ear pinna blood flow, after microinjection of 8-OH-DPAT (3-5 nmol in 300-500 nl) into the raphé, transferring the animal from a warm cage (25-28 degrees C) to a cold cage (5-10 degrees C) did not reduce the ear pinna flow (from 57 +/- 7 cm/s to 59 +/- 3 cm/s, P > 0.05, n = 5), unlike Ringer-treated animals. Microinjection of WAY-100635 (5 nmol in 500 nl) into the raphé reversed ear pinna flow changes induced by intravenous administration of 8-OH-DPAT (0.1 mg/kg, i.v.). In anesthetized rabbits with measuring postganglionic ear pinna sympathetic nerve activity, microinjection of 8-OH-DPAT (1-2 nmol in 100-200 nl) into the raphé reduced resting ear pinna sympathetic nerve activity to 14 +/- 4% of pre-injection level (P < 0.01, n = 12) and attenuated increases in ear pinna sympathetic nerve activity normally elicited by cooling the animal's trunk. WAY-100635 (2 nmol into 200 nl) into the raphé reversed inhibition of ear pinna sympathetic nerve activity elicited by 8-OH-DPAT (0.1 mg/kg, i.v.). The activation of 5-HT1A receptors expressed on the medullary raphé neurons results in reversal of cold-elicited cutaneous vasoconstriction possibly through inhibition of sympathetic premotor neurons that innervate sympathetic preganglionic neurons controlling cutaneous vasomotion.

Purpose: Structural and functional abnormalities in the tumor vascular network are considered factors of resistance of solid tumors to cytotoxic treatments. To increase the efficacy of anticancer treatments, efforts must be made to find new strategies for transiently opening the tumor vascular bed to alleviate tumor hypoxia (source of resistance to radiotherapy) and improve the delivery of chemotherapeutic agents. We hypothesized that Botulinum neurotoxin type A (BoNT-A) could interfere with neurotransmitter release at the perivascular sympathetic varicosities, leading to inhibition of the neurogenic contractions of tumor vessels and therefore improving tumor perfusion and oxygenation., Experimental Design: To test this hypothesis, BoNT-A was injected locally into mouse tumors (fibrosarcoma FSaII, hepatocarcinoma transplantable liver tumor), and electron paramagnetic resonance oximetry was used to monitor pO(2) in vivo repeatedly for 4 days. Additionally, contrast-enhanced magnetic resonance imaging was used to measure tumor perfusion in vivo. Finally, isolated arteries were mounted in wire myograph to monitor specifically the neurogenic tone developed by arterioles that were co-opted by the surrounding growing tumor cells., Results: Using these tumor models, we showed that local administration of BoNT-A (two sites; dose, 29 units/kg) substantially increases tumor oxygenation and perfusion, leading to a substantial improvement in the tumor response to radiotherapy (20 Gy of 250-kV radiation) and chemotherapy (cyclophosphamide, 50 mg/kg). This observed therapeutic gain results from an opening of the tumor vascular bed by BoNT-A because we showed that BoNT-A could inhibit neurogenic tone in the tumor vasculature., Conclusions: The opening of the vascular bed induced by BoNT-A offers a way to significantly increase the response of tumors to radiotherapy and chemotherapy.

This study was designed to investigate the dose-rate dependent effects of ionising radiation on endothelium- and NO-mediated reactivity of aorta and coronary vessels. Rats were exposed to acute ((137)Cs, 9 x 10(-4) Gy s(-1), 18 min) and chronic ((137)Cs, 2.8 x 10(-7) Gy s(-1), 41 days) radiation in 1 Gy dose. Acute irradiation transiently increased coronary flow in eNOS-activity-dependent manner on day 3 after exposure. In striking contrast, chronic irradiation caused a significant depression of coronary flow even on day 90 after irradiation and abolished the effects of NO-synthase inhibitor N-nitro-L-arginine methyl ester (10 micromol l(-1)). Furthermore, low intensity radiation strongly diminished the vasodilator properties of NO-donor sodium nitroprusside (5 micromol l(-1)). A similar pattern was observed in aortic rings. Endothelium-dependent vasodilation was increased on days 3 and 10 after acute irradiation, but strongly inhibited following chronic exposure for the entire post-radiation period. This was accompanied by a diminished vasodilator response to NO-donor on days 3, 10 and 30 of post-radiation but not on day 90. The data suggest that ionising radiation in 1 Gy induces changes of aortic and coronary vessels reactivity depending on the dose-rate and the interval after exposure.

Purpose: To investigate the action of ultra-low dose beta-radiation (ULDBR) on isolated segments of blood vessels., Materials and Methods: We used the pharmacological model of isolated rabbit carotid arteries with intact or mechanically removed endothelium. Specific vascular responses to beta-irradiation were registered after addition of (90)Sr in the concentration range between 12 and 96 microCi l(-1) to the organ bath containing physiological salt solution (PSS)., Results: Intact vascular rings, preconstricted with 20 mM K(+)-PSS, developed an additional constriction upon the addition of (90)Sr depending on the absorbed radiation dose (21.5, 42.9, 85.8, and 171.6 microGy) and the dose rate (51.5, 103.0, 206.0 and 412.0 microGy h(-1)). The vasoconstriction due to (90)Sr was absent in the endothelium-denuded vascular segments indicating the endothelium dependent action of ULDBR. Irradiation did not alter the endothelium dependent relaxation of rabbit carotid arteries induced by acetylcholine. The endothelium dependent responses to ULDBR were abolished after increasing the extra-cellular K(+) to 40 mM., Conclusions: ULDBR acts on rabbit carotid arteries as a pharmacological signalling agent because ULDBR effects were completely reversible. ULDBR-mediated contractile responses of the vessels are endothelium dependent. The resistance of acetylcholine endothelium-dependent relaxation of rabbit carotid arteries to ULDBR indicates that the polyphosphoinositide-nitric oxide (NO) signalling cascade is not impaired by ULDBR in endothelial cells.

Although no effects of permanent magnets on resting skin blood flow (SBF) in humans have yet been demonstrated, the possibility that magnet related effects might modify dynamic SBF changes has not been previously studied. We hypothesized that magnets may alter local neurovascular mechanisms to cause changes in normal SBF vasoactive responses. To test this, we studied the effects of a magnet on SBF reductions induced by sympathetic reflexes associated with deep inspirations. SBF was continuously monitored by a dual channel laser-Doppler flowmeter with probes on the middle finger dorsum of both hands of 24 healthy subjects. In the first of two successive intervals, each of the fingers rested on sham ceramic magnets (control interval). Subsequently, one finger rested on an active magnet and the other finger on a sham (experimental interval). Skin temperatures were also measured. The magnet was a 37 mm diameter x 14 mm thick ceramic magnet with a surface field strength of 85 mT measured in the geometrical center of the magnet. Field strength at the finger dorsum, 13 mm above magnet, was 31.5 mT. During each interval, three deep breaths were used to elicit SBF reductions. Responses were calculated as the percent reduction in SBF from its prior 20 s average. Breaths in each interval were spaced 3 min apart to permit full recovery between responses. The experimental interval started after an active magnet was in place for 20 min. Results showed no significant difference in either vasoconstrictive responses or skin temperature due to the magnet. We conclude that magnets of the type, strength and duration used, have no significant effect on vasoconstrictive processes associated with this sympathetic reflex in this group of healthy subjects., (Copyright 2005 Wiley-Liss, Inc.)

This study was designed to directly quantify the effect of localized static magnetic field (SMF) exposure on the diameter of microvessels in adult rat skeletal muscle in vivo. Microvascular networks in the exteriorized rat spinotrapezius microvasculature were exposed to a localized, uniform 70 mT SMF for 15 min. Arteriolar vessel diameters were measured; and the extent of vessel contraction, microvascular tone, was calculated before exposure, immediately after exposure, and 15 and 30 min after removal of the field. A calculated value of high tone corresponds to vessels that are vasoconstricted and a calculated value of low tone refers to vessels that are vasodilated. Vessels with initial tone <15% showed an increasing trend in tone and, conversely, vessels with initial tone >15% showed a significant (P < 0.05) decrease in tone 15 and 30 min following application, respectively. Further classification of the data with regards to the initial vessel diameter demonstrated that vessels with initial diameters <30 microm and initial tone <15%, smaller diameter vessels that are initially vasodilated, showed significant (P < 0.05) increase in tone immediately, 15 and 30 min following SMF exposure. Additionally, <30 microm vessels with >15% initial tone, smaller diameter vessels that are initially vasoconstricted, demonstrated a significant (P < 0.05) decrease in tone 30 min after SMF exposure. Vessels with initial diameters >30 microm had no significant response to the SMF. These results imply that SMF exposure influences arteriolar diameters, and therefore microvascular tone, in a restorative fashion acting to normalize the tone to the median tone value of 15% following exposure. Because this response occurs primarily in the resistance arterioles, which significantly influence tissue perfusion, SMF application could be efficacious for the treatment of both ischemic and edematous tissue disorders involving compromised microvascular function., (2004 Wiley-Liss, Inc.)

Purpose: To test the effects of irradiation (R*) on the pulmonary artery (PA)., Methods and Materials: Isolated PA rings were submitted to gamma irradiation (cesium, 8 Gy/min(-1)) at doses of 20 Gy-140 Gy. Rings were placed in an organ chamber, contracted with serotonin (10(-4) M 5-hydroxytryptamine [5-HT]), then exposed to acetylcholine (ACh) in incremental concentrations. Smooth muscle cell (SMC) membrane potential was measured with microelectrodes., Results: A high dose of irradiation (60 Gy) increased 5HT contraction by 20%, whereas lower (20 Gy) doses slightly decreased it compared with control. In the absence of the endothelium, 5-HT precontracted rings exposed to 20 Gy irradiation developed a dose-dependent relaxation induced by acetylcholine (EI-ACh) with maximal relaxation of 60 +/- 17% (n = 13). This was totally blocked by L-NAME (10(-4) M), partly by 7-nitro indazole; it was abolished by hypoxia and iberiotoxin, decreased by tetra-ethyl-ammonium, and not affected by free radical scavengers. In irradiated rings, hypoxia induced a slight contraction which was never observed in control rings. No differences in SMC membrane potential were observed between irradiated and nonirradiated PA rings., Conclusion: Irradiation mediates endothelium independent relaxation by a mechanism involving the nitric oxide pathway and K-channels.

Objectives: We sought to demonstrate that brachytherapy reduces coronary spasm in refractory and highly symptomatic variant angina., Background: In some patients with variant angina due to extensive vasoconstriction, intensive drug therapy fails to sufficiently relieve symptoms., Methods: In 18 patients with frequent angina episodes despite triple anti-anginal therapy, coronary spasm was induced by intracoronary acetylcholine (ACh) infusion. Five patients had spasm in a second vessel. Intracoronary radiation (20 Gy) was applied to vasospastic segments using a beta-emitting ((32)P) wire source centered within a Galileo balloon. Parameters of vessel function before and after brachytherapy were investigated., Results: Before brachytherapy, artery diameters decreased (p < 0.0001) from 2.8 +/- 0.4 mm to 1.0 +/- 0.4 mm for the first vessels and from 3.1 +/- 0.3 mm to 1.0 +/- 0.2 mm for the second vessels. After brachytherapy (143 +/- 106 and 80 +/- 52 days for first and second vessels, respectively), ACh-induced vasoconstriction was significantly reduced. The ACh-induced changes in artery diameter before and after brachytherapy were -1.5 +/- 0.5 mm and -0.5 +/- 0.3 mm (p < 0.0001) for the first vessels and -1.4 +/- 0.3 mm and -0.4 +/- 0.2 mm (p < 0.01) for the second vessels, respectively. In non-irradiated spastic vessels, ACh-induced vasoconstriction remained unchanged (e.g., -1.7 +/- 0.6 mm, -1.6 +/- 0.3 mm, and -1.5 +/- 0.5 mm for second vessels, at first investigation, first follow-up, and immediately before brachytherapy, respectively). Angina frequency decreased from 15.6 +/- 6.0 to 2.2 +/- 2.4 angina episodes/week (p < 0.001) in treated patients., Conclusions: Brachytherapy is a potential therapy in patients with highly symptomatic variant angina.

Purpose: Endovascular irradiation inhibits neointimal hyperplasia in ballooned and stented arteries but impacts both diseased and adjacent normal tissue. Little is known about the effects of irradiation on downstream vasculature. In this study, we investigated vascular function and structure of pig coronary arteries distal to sites of endoluminal irradiation., Materials and Methods: Vasomotor responses of distal arteries to contraction of KCl and PGF2alpha and endothelium-dependent (substance P and A23187) and -independent (sodium nitroprusside) relaxation were studied in naïve, sham-treated, irradiated, stented, and stented plus irradiated vessels. Light and scanning electron microscopy were used to assess vascular morphology., Results: Relaxations to substance P and A23187 at 1 month post treatment were significantly decreased in the irradiated group, whereas contractile response to PGF2alpha was significantly increased. Hemorrhage, mural thrombus, and inflammation were present at the upstream-irradiated site; inflammatory cells were also present adherent to the endothelium in the distal segments., Conclusions: Distal vasomotor function reflects an influence from the nature of a proximal intervention. The effect of irradiation on downstream conduit arteries to increase the threshold of contractility and suppress endothelium-dependent relaxation may be related to the presence of inflammatory cells at both the upstream-instrumented site as well as the distal location., (Copyright 2004 Elsevier Inc.)

Objective: After pelvic radiotherapy for gynecological cancer, changes in the vaginal epithelium might influence sexual arousal and satisfaction, leading to dyspareunia and relational problems. The aim of the study was to determine the feasibility of vaginal plethysmography in order to measure physical late effects of this therapy on sexual function., Methods: Patients treated with radiotherapy for cervical, endometrial, or ovarian cancer, who were in complete remission for over 1 year, underwent vaginal plethysmography to measure changes in vaginal vasocongestion, while watching erotic video fragments. Afterward two questionnaires, designed to measure feelings of sexual arousal during the video, and to identify sexual dysfunction, were completed. The results were compared with those of healthy women., Results: Patients (n = 9) and volunteers (n = 8) did not differ in baseline amplitude of plethysmography and showed comparable changes in vaginal vasocongestion during the various video fragments. The decline in amplitude during the last video fragment in the patient group did not reach significance, but the group of patients is small and heterogeneous. Addressing subjective sexual arousal during the video, patients reported less feelings of lust and desire and fewer bodily sensations while watching than the controls. Patients worried more about the sexual satisfaction of their partners than controls., Conclusion: Vaginal plethysmography can be used to measure vaginal vasocongestion in patients treated with radiotherapy to the proximal vagina. In this pilot study the changes of vaginal vasocongestion during sexual arousal between patients and healthy volunteers were not different. This correlates with a comparable sexual satisfaction, although patients reported less feelings of lust.

The postradiation changes of constriction effects of angiotensin II (Ang II) and angiotensin I (Ang I) on isolated preparations of thoracic aorta young and old rats which underwent gamma-irradiation in dose 1 Gy (137Cs, 9 x 10(-4) Gy/s) were investigated. It has been found, that the aging leads to the alteration of angiotensin receptors, which appears as changes in their density and/or sensitivity to action of agonist. With increase of age the activity of angiotensin-converting enzyme (ACE) in the wall of aorta is oppressed, and as a result, the level of local formation of Ang II and the constriction, caused by it are reduced. The inhibitory influence of endothelium on vasoconstriction effects of Ang II and Ang I in ontogenesis does not change. The influence of gamma-radiation in a dose of 1 Gy modifies the functional activity of the local vascular renin-angiotensin system (RAS): the sensitivity and/or density of angiotensin receptors and the activity of ACE increased the dilatation influences of endothelium were oppressed mainly for account of easing the synthesis of NO. The duration of postradiation infringements of functional activity of local vascular RAS in many respects are determined by the stage of ontogenic development of irradiated organism.

Acute effects of whole body exposure to static magnetic field (SMF) on pharmacologically induced hypertension in a conscious rabbit were evaluated. Hypertensive and vasoconstrictive actions were induced by norepinephrine (NE) or a nonselective nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-l-arginine methyl ester (l-NAME). The hemodynamics in a central artery of the ear lobe was measured continuously and analyzed by penetrating microphotoelectric plethysmography (MPPG). Concurrently, blood pressure (BP) changes in a central artery, contralateral to that of the MPPG measured ear lobe, were monitored. Magnetic flux densities were 5.5 mT (Bmax), the magnetic gradient peaked in the throat at the level of approximately 0.09 mT/mm, and the duration of exposure was 30 min. The results demonstrated that under normal physiological conditions without treatment of pharmacological agents, there were no statistically significant differences in the hemodynamics and BP changes between the sham and the SMF exposure alone. Under pharmacologically induced hypertensive conditions, the whole body exposure to nonuniform SMF with peak magnetic gradient in the carotid sinus baroreceptor significantly attenuated the vasoconstriction and suppressed the elevation of BPs. These findings suggest that antipressor effects of the SMF on the hemodynamics under NE or l-NAME induced high vascular tone might be, in part, dependent on modulation of NE mediated response in conjunction with alteration in NOS activity, thereby modulating BPs., (Copyright 2003 Wiley-Liss, Inc.)

The potential health risks of radiofrequency electromagnetic fields (EMFs) emitted by mobile phones are of considerable public interest. The present study investigated the hypothesis, based on the results of our previous study, that exposure to EMFs can increase sympathetic vasoconstrictor activity. Forty healthy young males and females underwent a single-blind, placebo-controlled protocol once on each of two different days. Each investigation included successive periods of placebo and EMF exposure, given in a randomized order. The exposure was implemented by a GSM-like signal (900 MHz, pulsed with 217 Hz, 2 W) using a mobile phone mounted on the right-hand side of the head in a typical telephoning position. Each period of placebo exposure and of EMF exposure consisted of 20 min of supine rest, 10 min of 70 degrees upright tilt on a tilt table, and another 20 min of supine rest. Blood pressure, heart rate and cutaneous capillary perfusion were measured continuously. In addition, serum levels of norepinephrine, epinephrine, cortisol and endothelin were analyzed in venous blood samples taken every 10 min. Similar to the previous study, systolic and diastolic blood pressure each showed slow, continuous, statistically significant increases of about 5 mmHg during the course of the protocol. All other parameters either decreased in parallel or remained constant. However, analysis of variance showed that the changes in blood pressure and in all other parameters were independent of the EMF exposure. These findings do not support the assumption of a nonthermal influence of EMFs emitted by mobile phones on the cardiovascular autonomic nervous system in healthy humans.

In vitro isometric small vessel myograph experiments and pathological investigations were performed on rat middle cerebral arteries. Thirty-four animals provided 68 normal vessels, six further rats had the endothelial layer mechanically removed from their 12 arteries. Eighteen animals received gamma knife irradiation to the middle cerebral arteries. Fifteen of these received 50 Gray, and three 25 Gray dose to the 50% isodose and the contralateral vessels offered 20 Gray and 15 Gray irradiated specimens. Survival times varied from 12 weeks to 18 months. In the acute stage, abolition of potassium-induced relaxation occurred as early as 24 h after irradiation whilst in one year this reaction seemed to recover and remained active to 18 months. The contraction response to prostaglandin F2 alpha was diminished at six weeks in the 50 Gray-irradiated vessels. However, from one year further reduction was seen and by 18 months this response was totally abolished. We demonstrated reduction of contractile capability of the irradiated normal vessels while the vessels remained patent. When using low irradiation dose there were no pathological changes even at 18 months, but marked physiological changes could be demonstrated. Different vessel wall functions appear to have different radiosensitivity, time course and capability for regeneration.

Acute effects of locally applied static magnetic fields (SMF) on pharmacologically altered blood pressure (BP) in a central artery of the ear lobe of a conscious rabbit were evaluated. Hypotensive and vasodilator actions were induced by a Ca(2+) channel blocker, nicardipine (NIC). Hypertensive and vasoconstrictive actions were induced by a nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME). The hemodynamic changes in the artery exposed to SMF were measured continuously and analyzed by penetrating microphotoelectric plethysmography (MPPG). Concurrently, BP changes in a central artery contralateral to that of the exposed ear lobe were monitored. SMF intensity was 1 mT and the duration of exposure was 30 min. A total of 180 experimental trials were carried out in 34 healthy adult male rabbits weighing 2.6-3.8 kg. Six experimental procedures were chosen at random: (1) sham exposure without pharmacological treatment; (2) SMF exposure alone; (3) decreased BP induced by a single intravenous (iv) bolus injection of NIC (100 microM/kg) without SMF exposure; (4) decreased BP induced by injection of NIC with SMF exposure; (5) increased BP induced by a constant iv infusion of L-NAME (10 mM/kg/h) without SMF exposure; (6) increased BP induced by infusion of L-NAME with SMF exposure. The results demonstrated that SMF significantly reduced the vasodilatation with enhanced vasomotion and antagonized the reduction of BP via NIC-blocked Ca(2+) channels in vascular smooth muscle cells. In addition, SMF significantly attenuated the vasoconstriction and suppressed the elevation of BP via NOS inhibition in vascular endothelial cells and/or central nervous system neurons. These results suggest that these modulatory effects of SMF on BP might, in part, involve a feedback control system for alteration in NOS activity in conjunction with modulation of Ca(2+) dynamics., (Copyright 2001 Wiley-Liss, Inc.)

Purpose: Ionizing irradiation inhibits restenosis in animal models and human. Vasomotor tone preservation during and after radiation therapy is of clinical importance. We therefore investigated vascular reactivity following radiation therapy., Methods and Materials: Wistar Sabra rats were treated with a single dose of 1000 cGy external X-ray irradiation. Vascular reactivity of 192 segments of rat thoracic aorta was studied in vitro in four groups (12 rats in each group, four segments from each aorta). Immediately after in vivo irradiation, immediately after ex vivo irradiation, 1 month after irradiation, and no irradiation (control)., Results: Vasoconstriction to phenylephrine (PE) 10(-9)-10(-5) M or KCl 118.0 mM in all the irradiated groups was similar to controls. Endothelium-dependent vasorelaxation to acetylcholine (ACh) 10(-9)-10(-5) M in segments studied immediately after in vivo irradiation was increased compared to controls at all concentrations (109.7+/-35. and 90.0+/-40.0%, respectively, at 10(-5) M, P=.006). Endothelium-independent relaxation to nitroglycerin 10(-9)-10(-5) M in all irradiated groups was similar to controls., Conclusions: External-ionizing irradiation with 1000 cGy in the rat aortic model induces acute and transient increase in endothelium-dependent relaxation to ACh, and does not alter vasoconstriction and endothelium-independent relaxation.

Despite a critical role for calcium in endothelial regulation of cerebrovascular tone, endothelial intracellular calcium ([Ca(2+)](i)) has never been measured in the context of an intact pressurized cerebral vessel. The purpose of the present study was to selectively measure endothelial or smooth muscle [Ca(2+)](i) and diameter in a pressurized/perfused cerebral vessel. In a pressurized rat middle cerebral artery, fura-2 AM was administered selectively to either the luminal (endothelium) or abluminal (smooth muscle) side of the vessel. Selectivity of loading was determined by measuring fura-2 fluorescence before and after removal of the endothelium. Removal of the endothelium virtually eliminated fura-2 fluorescence. In addition, 2-methylthioadenosine triphosphate (2MeS-ATP, a selective endothelial P2 receptor agonist) was used to infer the selectivity of fura-2 loading. It was reasoned that 2MeS-ATP should produce a decrease in smooth muscle [Ca(2+)](i) and an increase in endothelial [Ca(2+)](i) in selectively loaded vessels, consistent with its role as an NO-dependent dilator. In smooth muscle loaded vessels, [Ca(2+)](i) went from 252+/-8 to 82+/-9 nM following luminal administration of 2MeS-ATP, whereas in endothelial loaded vessels, [Ca(2+)](i) went from 137+/-11 to 271+/-20 nM. Thus, a method is provided which allows for selective measurement of endothelial or smooth muscle [Ca(2+)](i) with simultaneous measurement of diameter in a pressurized cerebral vessel.

Object: Ultraviolet (UV) light irradiation can lead to immunomodulation. The purpose of this study was to determine the preventive effect of UV light on cerebral vasospasm by using a rabbit common carotid artery (CCA) model., Methods: Rabbit CCAs were constricted for a long period by application of autologous blood within a silicon sheath. Before immersion in blood, the CCAs were adventitiously exposed to UV light emitted from a helium-cadmium laser (wavelength 325 nm) yielding an irradiation energy of 10 mJ/mm2. The occurrence of vasospasm was evaluated using angiography 48 hours after blood exposure in this model. The UV light treatment significantly reduced the degree of vasospasm. Compared with luminal diameters measured on Day 0, prior to treatment, the luminal diameters of UV light-treated arteries (six animals) decreased by only 6%, whereas that of the sham-treated arteries (eight animals) significantly decreased by 26% (p<0.001). Histological examination of UV light-treated CCAs revealed no endothelial damage and extended smooth-muscle cells, in which some fragmented nuclei were confirmed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. Twenty-eight days after blood exposure, examination of UV light-treated CCAs revealed only myointimal proliferation, similar to that of the sham-treated CCAs., Conclusions: These results are the first to provide evidence of a prophylactic effect of UV light on vasospasm and are suggestive of involvement of apoptosis in the mechanism of this effect.

We applied low-power ultraviolet (UV) laser irradiation via a thin flexible optical fiber to an in vivo model of vasospasm using an intravascular transluminal approach. The surgically exposed left femoral arteries of a rabbit were constricted by norepinephrine. A quartz fiber of 400 microm in diameter was introduced into the artery via the right common carotid artery through a 2.5F catheter. The femoral artery lumen was then irradiated with a helium-cadmium laser (wavelength 325 nm, output power 8 mW) through the fiber for 30 s. The UV irradiation increased the mean luminal diameter by 85% in comparison to the precontracted state, while the increase was only 45% in a sham operation. A histopathologic examination revealed no thermal damage and an intact internal elastic lamina. These results suggest that intravascular transluminal irradiation with a low-power UV laser may thus have potentially clinical applications to reverse acute arterial vasospasm.

Several studies have reported thrombus formation and/or the release of specific vasoactive eicosanoids, suggesting that platelet activation or damage after photodynamic therapy (PDT) may contribute to blood flow stasis. The role of circulating platelets on blood flow stasis and vascular leakage of macromolecules during and after PDT was assessed in an intravital animal model. Sprague-Dawley rats bearing chondrosarcoma on the right hind limb were injected intravenously (i.v.) with 25 mg/kg Photofrin 24 h before light treatment of 135 J/cm2 at 630 nm. Thrombocytopenia was induced in animals by administration of 3.75 mg/kg of rabbit anti-rat platelet antibody i.v. 30 min before the initiation of the light treatment. This regimen reduced circulating platelet levels from 300,000/mm3 to 20,000/mm3. Reductions in the luminal diameter of the microvasculature in normal muscle and tumor were observed in control animals given Photofrin and light. Venule leakage of macromolecules was noted shortly after the start of light treatment and continued throughout the period of observation. Animals made thrombocytopenic showed none of these changes after PDT in either normal tissues or tumor. The lack of vessel response correlated with the absence of thromboxane release in blood during PDT. These data suggest that platelets and eicosanoid release are necessary for vessel constriction and blood flow stasis after PDT using Photofrin.

The middle cerebral artery (MCA) was irradiated in 94 rats using the Gamma Knife. The vessels receiving 20, 50, 80 and 200 Gy were removed 24 h later and mounted on a myograph. Contractility responses to potassium and prostaglandin (PG) F2 alpha were tested. After precontraction with PGF2 alpha, the relaxant effects of histamine, papaverine, L-arginine and sodium nitroprusside were examined. Other vessels were preincubated with ouabain or N omega-nitro-L-arginine methyl ester before testing with the relaxant agents. After irradiation, the contractile response to maximal potassium and PGF concentrations was diminished, suggesting dose-dependent radiation damage to the contractile mechanism. The normal MCA shows an initial relaxation in the presence of a low K+ concentration, which is Na+, K(+)-ATPase dependent. According to this study, the endothelium-derived relaxation function was suppressed by radiation, suggesting that there is an early change in irradiated vessels, demonstrable by functional studies, which affects both the smooth muscle and endothelial layers.

This report concerns a pilot study of the short- and long-term effects of gamma knife radiosurgery on vascular responses. The investigation was carried out on male Sprague-Dawley rats, and the relaxation and contraction responses of the right common carotid artery (CCA) were assessed following irradiation (100 Gy). The non-treated CCA of the same animals served as internal controls. Non-irradiated rats were used to control the effect of normal aging on vascular function. Isometric tension was determined on in vitro preparations of arterial rings. Acetylcholine-mediated, endothelium-dependent relaxation was impaired one month after radiosurgery, as was endothelium-independent relaxation induced by sodium nitroprusside, but the effect on the latter was minimal. The irradiated CCA was also impaired with respect to contraction responses induced by norepinephrine, endothelin-1 or phorbol dibutyrate. This impairment appeared to be biphasic, as it was evident one day after radiosurgery, followed by a partial recovery one week later, and again manifest after one month. At the light microscope level, the carotid arteries appeared to be well preserved throughout the experiment. However, obvious ultrastructural changes were noted in endothelial and smooth muscle cells of specimens obtained three months after radiosurgery. The present data indicate that high dose gamma knife radiosurgery affects the functions of both, the vascular endothelium and the vascular smooth muscles in an apparent time-dependent fashion. Because of its increasing application to patients, there is the need for studying the effects of gamma knife radiosurgery on cerebral arteries, since functional vascular changes may occur in the absence of obvious histological alterations. Our results on CCAs point to the feasibility of such experimental investigations.