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Background: The gap between the supply of organs available for transplantation and demand is growing, especially among ethnic groups.Objective: To evaluate the effect of a video designed to address concerns of ethnic groups about organ donation.Design: Cluster randomized, controlled trial. Randomization was performed by using a random-number table with centralized allocation concealment. Participants and investigators assessing outcomes were not blinded to group assignment. (ClinicalTrials.gov registration number: NCT00870506)Setting: Twelve branches of the Ohio Bureau of Motor Vehicles in northeastern Ohio.Participants: 952 participants aged 15 to 66 years.Intervention: Video (intervention; n = 443) or usual Bureau of Motor Vehicles license practices (control; n = 509).Measurements: The primary outcome was the proportion of participants who provided consent for organ donation on a newly acquired driver's license, learner's permit, or state identification card. Secondary outcomes included willingness to make a living kidney donation to a family member in need and personal beliefs about donation.Results: More participants who viewed the video consented to donate organs than control participants (84% vs. 72%; difference, 12 percentage points [95% CI, 6 to 17 percentage points]). The video was effective among black participants (76% vs. 54%; difference, 22 percentage points [CI, 9 to 35 percentage points]) and white participants (88% vs. 77%; difference, 11 percentage points [CI, 5 to 15 percentage points]). At the end of the trial, fewer intervention than control participants reported having insufficient information about organ donation (34% vs. 44%; difference, -10 percentage points [CI, -16 to -4 percentage points]), wanting to be buried with all of their organs (14% vs. 25%; difference, -11 percentage points [CI, -16 to -6 percentage points]), and having conflicts with organ donation (7% vs. 11%; difference, -4 percentage points [CI, -8 to -2 percentage points]).Limitation: How the observed increases in consent to donate organs might translate into a greater organ supply in the region is unclear.Conclusion: Exposure to a brief video addressing concerns that ethnic groups have about organ donation just before obtaining a license, permit, or identification card increased consent to donate organs among white and black participants.Primary Funding Source: National Institutes of Health and the Robert Wood Johnson Foundation. [ABSTRACT FROM AUTHOR]

Non-typhoid Salmonella enterica causes salmonellosis illness, and this bacterium can contaminate food throughout the production chain, including those that are consumed as raw products. Salmonella enterica can adhere to and internalize into fresh produce such as cherry tomatoes. It has been reported that lytic bacteriophages (phages) can be used as a biocontrol agent in the agricultural field, being an alternative for the control of Salmonella in red meat, fish, lettuce, and cabbage. The aim of this study was to characterize the two phages present in the PHA46 cocktail to determine their morphology, genome, host range, and resistance to different temperatures and pHs values; and later evaluate their lytic activity to reduce the adherence to and internalization of Salmonella enterica serovars Newport and Typhimurium into cherry tomatoes. In addition, in this work, we also explored the effect of the PHA46 cocktail on the virulence of S. Newport-45 and S. Typhimurium SL1344, recovered from the interior of cherry tomatoes, on the lifespan of the animal model Caenorhabditis elegans. The nematode C. elegans, recently has been used to test the virulence of Salmonella and it is easy to maintain and work with in the laboratory. The results revealed that the morphology obtained by Transmission Electron Microscopy of two phages from the PHA46 cocktail correspond to a myovirus, the analyses of their genomes sequences did not report virulence or antimicrobial resistance genes. The PHA46 sample is specific for 33 different serovars from different Salmonella strains and shows stability at 7 °C and pH 6. Also, the PHA46 cocktail was effective in reducing the adherence of S. Newport-45 and S. Typhimurium SL1344 to cherry tomatoes, at an average of 0.9 log 10 , respectively. Regarding internalized bacteria, the reduction was at an average of 1.2 log 10 , of the serovars mentioned above. The lifespan experiments in C. elegans showed by itself, that the PHA46 cocktail was harmless to the nematode, and the virulence from both Salmonella strains grown in vitro is diminished in the presence of the PHA46 cocktail. In conclusion, these results showed that the PHA46 cocktail could be a good candidate to be used as a biocontrol agent against Salmonella enterica., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Controlled donation after circulatory determination of death (cDCD) seems an effective way to mitigate the critical shortage of available organs for transplant worldwide. As a recently developed procedure for organ retrieval, some questions remain unsolved such as the uncertainty regarding the effect of functional warm ischemia time (FWIT) on organs´ viability., Methods: We developed a multicenter prospective cohort study collecting all data from evaluated organs during cDCD from 2017 to 2020. All the procedures related to cDCD were performed with normothermic regional perfusion. The analysis included organ retrieval as endpoint and FWIT as exposure of interest. The effect of FWIT on the likelihood for organ retrieval was evaluated with Relative distribution analysis., Results: A total amount of 507 organs´ related information was analyzed from 95 organ donors. Median donor age was 62 years, and 63% of donors were male. Stroke was the most common diagnosis before withdrawal of life-sustaining therapy (61%), followed by anoxic encephalopathy (21%). This analysis showed that length of FWIT was inversely associated with organ retrieval rates for liver, kidneys, and pancreas. No statistically significant association was found for lungs., Conclusions: Results showed an inverse association between functional warm ischemia time (FWIT) and retrieval rate. We also have postulated optimal FWIT's thresholds for organ retrieval. FWIT for liver retrieval remained between 6 and less than 11 min and in case of kidneys and pancreas, the optimal FWIT for retrieval was 6 to 12 min. These results could be valuable to improve organ utilization and for future analysis., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Objectives: Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein., Methods: Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths. Concentration-response curves to ranolazine were constructed in rings precontracted with phenylephrine, endothelin-1, vasopressin, KCl and the thromboxane A2 analogue U-46619. In rings precontracted with phenylephrine, relaxation to ranolazine was tested in the absence and presence of endothelial factors inhibitors, K+ channel blockers and verapamil. The effects of ranolazine on frequency-response and concentration-response curves to phenylephrine were performed in the absence and presence of endothelial factors inhibitors and K+ channel blockers. Endothelial nitric oxide synthase, α1 adrenergic receptor and large conductance Ca2+-activated K+ channel protein expressions were measured by Western blotting., Results: Ranolazine (10-9-10-4 M) produced a concentration-dependent relaxation only in rings precontracted with phenylephrine that was reduced by endothelial denudation, NG-nitro-l-arginine methyl ester (10-4 M), charybdotoxin (10-7 M) and verapamil (10-6 M). Ranolazine diminished adrenergic contractions induced by electrical field stimulation (2-4 Hz) and phenylephrine (10-9-10-5 M) that were prevented by tetraethylammonium (10-3 M) and charybdotoxin (10-7 M). Ranolazine significantly decreased α1 adrenergic receptor and increased large conductance Ca2+-activated K+ channel protein expression in the saphenous vein., Conclusions: Ranolazine diminishes the adrenergic vasoconstriction, acting as α1 antagonist, and by increasing large conductance Ca2+-activated K+ channel involvement. The relaxant effects of ranolazine are partially mediated by endothelial nitric oxide, large conductance Ca2+-activated K+ channels and the blockade of voltage-dependent Ca2+ channels., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Hemodialysis patients' ability to access food that is both compatible with a renal diet and affordable is affected by the local food environment. Comparisons of the availability and cost of food items suitable for the renal diet versus a typical unrestricted diet were completed using the standard Nutrition Environment Measures Survey and a renal diet-modified Nutrition Environment Measures Survey., Design: Cross-sectional study., Setting: Twelve grocery stores in Northeast Ohio., Main Outcome Measure: Availability and cost of food items in 12 categories., Results: The mean total number of food items available differed significantly (P ≤ .001) between the unrestricted diet (38.9 ± 4.5) and renal diet (32.2 ± 4.7). The mean total cost per serving did not differ significantly (P = 0.48) between the unrestricted diet ($5.67 ± 2.50) and renal diet ($5.76 ± 2.74)., Conclusion: The availability of renal diet food items is significantly less than that of unrestricted diet food items, but there is no difference in the cost of items that are available in grocery stores. Further work is needed to determine how to improve the food environment for patients with chronic diseases., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to test the ability of a newly developed nutrition algorithm on (1) clinical utility and (2) ability to capture patient outcomes., Research Design: This was a prospective observational study, using a practice based research network structure, involving renal dietitians and hemodialysis [HD] patients., Setting: This study took place in HD outpatient units in five different countries., Subjects: Hundred chronic HD patients were included in this study. To select subjects, dietitians screened and consented patients in their facilities until 4 patients "at nutrition risk" based on the algorithm screening tool were identified. Inclusion criteria were patients aged older than 19 years, not on hospice or equivalent, able to read the informed consent and ask questions, and receiving HD., Main Outcome Measure: The ability of the algorithm screening tool is to identify patients at nutrition risk, to guide clinicians in logical renal-modified nutrition care process chains including follow-up on relevant parameters, and capture change in outcomes over 3 months. Statistics were performed using SPSS version 20.0 and significance was set at P < .05., Results: One hundred patients on HD, enrolled by 29 dietitians, were included in this analysis. The average number of out-of-range screening parameters per patient was 3.7 (standard deviation 1.5, range 1-7), and the most prevalent risk factors were elevated parathyroid hormone (PTH; 62.8%) and low serum cholesterol (56.5%). At the initial screening step, 8 of the 14 factors led to chains with nonrandom selection patterns (by χ(2) test with P < .05). In the subsequent diagnosis step, patients diagnosed within the insufficient protein group (n = 38), increased protein intake by 0.11 g/kg/day (P = .022). In patients with a diagnosis in the high PTH group, PTH decreased by a mean of 176.85 pg/mL (n = 19, P = .011) and in those with a diagnosis in the high phosphorous group, serum phosphorous decreased by a mean of 0.91 mg/dL (n = 33, P = .006). Finally, the relative likelihood of each assessment being completed after making the related diagnosis at the previous visit compared with those for whom that diagnosis was not made was assessed, including the likelihood of a patient's protein intake assessed after a diagnosis in the insufficient protein group was made (odds ratio = 4.08, P < .05)., Conclusions: This study demonstrates the clinical utility of a web-based HD-specific nutrition algorithm, including the ability to track changes in outcomes over time. There is potential for future research to use this tool and investigate the comparative impact of nutrition interventions., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: In the present study we investigated the intervention of nitric oxide and prostacyclin in the responses to vasopressin of isolated thyroid arteries obtained from multi-organ donors., Main Methods: Paired artery rings from glandular branches of the superior thyroid artery, one normal and the other deendothelised, were mounted in organ baths for isometric recording of tension. Concentration-response curves to vasopressin were determined in the absence and in the presence of either the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP (10(-8)M), the nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine (L-NMMA, 10(-4)M), or the inhibitor of prostaglandins indomethacin (10(-6)M)., Key Findings: In artery rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions. The vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP (10(-8)M) displaced the control curve to vasopressin 19-fold to the right in a parallel manner. The contractile response to vasopressin was unaffected by L-NMMA or by indomethacin., Significance: Vasopressin causes constriction of human thyroid arteries by stimulation of V1 vasopressin receptors located on smooth muscle cells. These effects are not linked to the presence of an intact endothelium or to the release of nitric oxide or prostaglandins. The constriction of thyroid arteries may be particularly relevant in certain pathophysiological circumstances in which vasopressin is released in amounts that could interfere with the blood supply to the thyroid gland., (© 2013.)

Objective: The objective of this study was to determine the prevalence of phosphorus-containing food additives in best-selling processed grocery products and to compare the phosphorus content of a subset of top-selling foods with and without phosphorus additives., Design: The labels of 2394 best-selling branded grocery products in northeast Ohio were reviewed for phosphorus additives. The top 5 best-selling products containing phosphorus additives from each food category were matched with similar products without phosphorus additives and analyzed for phosphorus content. Four days of sample meals consisting of foods with and without phosphorus additives were created, and daily phosphorus and pricing differentials were computed., Main Outcome Measures: Presence of phosphorus-containing food additives, phosphorus content., Results: Forty-four percent of the best-selling grocery items contained phosphorus additives. The additives were particularly common in prepared frozen foods (72%), dry food mixes (70%), packaged meat (65%), bread and baked goods (57%), soup (54%), and yogurt (51%) categories. Phosphorus additive-containing foods averaged 67 mg phosphorus/100 g more than matched nonadditive-containing foods (P = .03). Sample meals comprised mostly of phosphorus additive-containing foods had 736 mg more phosphorus per day compared with meals consisting of only additive-free foods. Phosphorus additive-free meals cost an average of $2.00 more per day., Conclusion: Phosphorus additives are common in best-selling processed groceries and contribute significantly to their phosphorus content. Moreover, phosphorus additive foods are less costly than phosphorus additive-free foods. As a result, persons with chronic kidney disease may purchase these popular low-cost groceries and unknowingly increase their intake of highly bioavailable phosphorus., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: This study was designed to evaluate the psychometric attributes and screening efficiency of a Spanish version of the Children Predictive Scales (DPS) against the Spanish Diagnostic Interview Schedule for Children (DISC-IV)., Method: This pilot cross-sectional study included 61 children aged 9 to 14 years in a mainstream school. The following psychometric attributes were analyzed: acceptability, scale assumptions, internal consistency, and precision, as well the predictive validity (AUC)., Results: The scale did not show ceiling or floor effects (6.4%, 1.3%, respectively). The internal consistency was high (α=0.92), and the standard error of measurement was adequate (SEM=1.54). The overall DPS AUC was 0.72 against DISC IV corresponding diagnosis., Conclusion: The Spanish version of the DPS-4.32 seems to be a reliable and precise tool for screening mental health disorders in a school-age population.

Background: We studied the participation of K(+) channels on the adrenergic responses in human saphenous veins as well as the intervention of dihydropyridine-sensitive Ca(2+) channels on modulation of adrenergic responses by K(+) channels blockade., Methods: Saphenous vein rings were obtained from 40 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension., Results: Iberiotoxin (10(-7) mol/L), an inhibitor of large conductance Ca(2+)-activated K(+) channels, and charybdotoxin (10(-7) mol/L), an inhibitor of both large and intermediate conductance Ca(2+)-activated K(+) channels, enhanced the contractions elicited by electrical field stimulation and produced a leftward shift of the concentration-response curve to norepinephrine. In contrast, the inhibitor of small conductance Ca(2+)-activated K(+) channels apamin (10(-6) mol/L) did not modify the contractile response to electrical field stimulation or norepinephrine. In the presence of the dihydropyridine Ca(2+)-channel blocker nifedipine (10(-6) mol/L), iberiotoxin and charybdotoxin failed to enhance the contractile responses to electrical field stimulation and norepinephrine., Conclusions: The results suggest that large conductance Ca(2+)-activated K(+) channels are activated by stimulation with norepinephrine to counteract the adrenergic-induced contractions of human saphenous vein. Thus, inhibition of these channels increases significantly the contraction, an effect that appears to be mediated by an increase in Ca(2+) entry through L-type voltage-dependent Ca(2+) channels.

Background: We recently reported that endothelium-dependent relaxation is impaired in forearm veins from patients with chronic renal failure. However, assessment of responses to norepinephrine remains controversial. We examined the contractile response to norepinephrine in forearm veins from patients on chronic hemodialysis and the role of nitric oxide (NO), prostanoids, and Ca(2+)-activated K(+) channels in this response., Methods: Isometric contraction curves were obtained in rings of forearm vein from 21 dialyzed patients and 12 multiorgan donors in response to norepinephrine (1 nmol/L to 10 micromol/L) or KCl (5 to 100 mmol/L)., Results: Veins from uremic patients were markedly less responsive to norepinephrine (7.6 +/- 0.6 g) and KCl (6.0 +/- 0.3 g) than those from organ donors (12.0 +/- 0.7 g and 10.4 +/- 0.5 g, respectively, P < .05). Treatment with N(G)-monomethyl-l-arginine (100 micromol/L), an inhibitor of NO synthase, or indomethacin (10 micromol/L), an inhibitor of prostacyclin synthesis, increased the response to norepinephrine in veins from control subjects but not in veins from dialyzed patients. Additional blockade of Ca(2+)-activated K(+) channels did not correct the hyporesponsiveness. In veins incubated in Ca(2+)-free solution containing either 100 mmol/L KCl or 1 micromol/L norepinephrine, addition of calcium chloride (0.1 to 30 mmol/L) elicited contractile responses that were significantly lower in veins from dialyzed patients., Conclusions: The results demonstrate that norepinephrine-mediated contractions of forearm veins are markedly decreased in dialyzed patients. Endothelium-derived relaxing factors are not involved in this effect. The reduced contractile response is most likely caused by a decreased calcium entry through voltage- and receptor-dependent calcium channels.

We measured cyclic GMP formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside (SNP) in pulmonary arteries obtained from 13 multi-organ donors. Sildenafil (10(-9)-10(-4) M) caused concentration-dependent relaxations and amplified the relaxation induced by SNP. Relaxation was unaffected by endothelium removal or by pre-treatment with the inhibitor of nitric oxide synthase L-NMMA (10(-4) M). SNP (10(-7) M) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10(-6) M). Thus, the enhancement of SNP-induced relaxation by sildenafil is mainly due to an increase in cyclic GMP accumulation.

Objective: We studied the intervention of nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) in mediating responses to acetylcholine in thyroid arteries from euthyroid and methimazole-treated (MT) patients., Design and Methods: Branches of the superior thyroid artery were obtained from 19 euthyroid patients and 17 MT patients (euthyroid at the time of surgery) undergoing total thyroidectomy or hemithyroidectomy. Artery rings were suspended in organ baths for isometric recording of tension., Results and Conclusions: Acetylcholine caused endothelium-dependent relaxation of greater magnitude in arteries from MT patients (pD(2) (-log EC(50)) values were 7.68 +/- 0.19 in euthyroid and 8.17 +/- 0.26 in MT patients, P < 0.05). The relaxation was unaffected by indomethacin and was partially reduced by the NO-synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). This reduction was higher in arteries from MT patients (50 +/- 6%) as compared with euthyroid patients (36 +/- 6%) (P < 0.05). Inhibition of K(+) channels using apamin combined with charybdotoxin or high K(+) solution abolished the relaxation resistance to L-NMMA and indomethacin. The maximal contraction response to noradrenaline (as a percentage of the response to 100 mM KCl) was lower in MT than in euthyroid patients (57 +/- 10 and 96 +/- 8 respectively, P < 0.05). The hyporesponsiveness to noradrenaline in arteries from MT patients was corrected by L-NMMA. The results indicate that: (i) thyroid arteries from MT patients show an increased relaxation response to acethylcholine and a decreased contraction response to noradrenaline due to overproduction of NO; (ii) EDHF plays a prominent role in acetylcholine-induced relaxation through activation of Ca(2+)-activated K(+) channels; (iii) the abnormal endothelium-dependent responses in arteries from MT patients are not corrected by medical treatment.

Background: In arteries, agonists such as acetylcholine release an endothelium-derived hyperpolarizing factor (EDHF) that is neither nitric oxide nor prostacyclin., Objectives: To examine the responses to acetylcholine in segments of forearm veins from patients with chronic renal failure who either had never received dialysis or had undergone long-term dialysis, and to determine the contribution of nitric oxide and EDHF to endothelium-dependent relaxation in veins from patients with chronic renal failure., Methods: Isometric tension was recorded in rings of forearm vein from 34 non-dialysed patients, 27 dialysed patients and 14 multiorgan donors (controls)., Results: Relaxation in response to acetylcholine was reduced in veins of non-dialysed and dialysed patients. The inhibitors of nitric oxide synthase NG-monomethyl-l-arginine (l-NMMA) and NG,NG-dimethyl-l-arginine (ADMA) reduced by 50% the maximum relaxation in response to acetylcholine in veins from controls and non-dialysed patients; the remaining relaxation was inhibited by 20 mmol/l KCl or by the K+ channel blockers tetraethylammonium chloride, iberiotoxin, charybdotoxin and the combination of barium plus ouabain, but not by apamin or glibenclamide. Relaxation in veins from dialysed patients was inhibited by K+ channel blockade but not by l-NMMA or ADMA., Conclusions: The results demonstrate that the endothelium-dependent relaxation in forearm veins from controls and non-dialysed patients is mediated by release of nitric oxide and EDHF. In contrast, the relaxation in veins from dialysed patients is mediated mainly by EDHF. EDHF-induced relaxation involves activation of large-conductance Ca2+-activated K+ channels.

Background: The objective of this study was to characterize the neurogenic contraction and relaxation of the human gastroepiploic artery and to determine whether the responses are mediated by nitric oxide (NO) from neural or endothelial origin., Methods: Rings of human gastroepiploic artery were obtained from 18 patients (12 men, 6 women) undergoing gastrectomy. The rings were suspended in organ baths for isometric recording of tension. We studied the contractile and relaxant responses to electrical field stimulation., Results: In arteries under resting conditions, electrical field stimulation (2 to 8 Hz) caused frequency-dependent contractions that were of greater magnitude in arteries denuded of endothelium and blocked by tetrodotoxin (10(-6) mol/L). The inhibitor of NO synthesis N(G)-monomethyl-L-arginine (L-NMMA, 10(-4) mol/L) increased contractile responses only in arteries with endothelium. In preparations contracted with norepinephrine in the presence of guanethidine (10(-6) mol/L) and atropine (10(-6) mol/L), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NMMA (10(-4) mol/L) and tetrodotoxin (10(-6) mol/L), but was unaffected by removal of the endothelium., Conclusions: The results provide functional evidence that NO is released by autonomic nerves of the human gastroepiploic artery. We hypothesize that the release of NO from both endothelial and neurogenic origin may modulate resistance of the human gastroepiploic artery. Dysfunction in any of these sources of NO should be considered in some form of vasospasm.

Background: This study was designed to measure cyclic guanosine 3'5' monophosphate (cGMP) formation and relaxation response to sildenafil given either alone or in combination with sodium nitroprusside in saphenous veins obtained from normotensive and hypertensive patients., Methods: Saphenous vein rings were obtained from 13 hypertensive and nine normotensive patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. The effect of sildenafil on sodium nitroprusside-induced cGMP formation was also assessed., Results: Sildenafil (10 nmol/L to 100 micromol/L) and sodium nitroprusside (0.01 to 100 nmol/L) caused concentration-dependent relaxations that were of greater magnitude in veins from normotensive patients. Sildenafil (1 to 10 micromol/L) amplified the relaxation induced by sodium nitroprusside in both groups of veins, but this effect was more pronounced in veins from hypertensive patients. Levels of cGMP in response to sodium nitroprusside were significantly lower in veins from hypertensive subjects. However, in the presence of sildenafil, the increase in cGMP levels in response to sodium nitroprusside was significantly greater in the hypertensive as compared with the normotensive group., Conclusions: Although the relaxant effects of sildenafil are less pronounced in veins from hypertensive patients, the synergistic interaction sildenafil-sodium nitroprusside is more effective in veins from hypertensive patients, mainly due to an increase in cGMP accumulation.

We studied the relaxant effects of milrinone, an inhibitor of phosphodiesterase 3, and rolipram, an inhibitor of phosphodiesterase 4, on contracted human penile dorsal artery and deep dorsal vein. Vascular rings from 12 multi-organ donors were suspended in organ baths for isometric recording of tension. Both milrinone and rolipram inhibited (100%) the contraction induced by noradrenaline and shifted the relaxation-response curves to the cAMP forming agents prostaglandin E(1) and forskolin to the left. The findings indicate that the cAMP pathway appears to be a main determinant of relaxation in human penile vessels.

Urocortin, an endogenous peptide structurally related to corticotropin-releasing factor (CRF), has potent cardiovascular effects, suggesting that it may be of significance in cardiovascular regulation. The objective of this study was to analyse the effects of urocortin and its action mechanisms on human blood vessels. To this, 3 mm long segments from human saphenous veins were prepared for isometric tension recording in an organ bath. In the segments at basal resting tone, urocortin did not produce any effect, but in the segments precontracted with endothelin-1 (1 - 10 nM), urocortin (1 pM - 10 nM) produced concentration-dependent relaxation. This relaxation was not modified by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (L-NAME, 100 microM), but it was potentiated by the cyclo-oxygenase inhibitor meclofenamate (10 microM) and it was reduced by the inhibitors of high-conductance Ca2+-dependent potassium channels tetraethylammonium (TEA, 10 mM) and charybdotoxin (100 nM). These results indicate that human saphenous veins are very sensitive to urocortin, which produces vascular relaxation by a mechanism independent of nitric oxide and dependent of high-conductance Ca2+-dependent potassium channels, and that it may be opposed by the release of vasoconstrictor prostanoids. Therefore, urocortin may be of significance for regulation of the venous circulation in humans.

Objective: We investigated the potentiating effect of U-46619, a synthetic analogue of thromboxane A(2) (TXA(2)), on the adrenergic responses in human saphenous vein., Methods: Saphenous vein rings were obtained from 35 patients undergoing coronary artery bypass surgery. The rings were suspended in organ bath chambers for isometric recording of tension., Results: U-46619 (10(-10)-3 x 10(-7) mol/l) produced concentration-dependent and endothelium-independent contractile responses. U-46619 (10(-10) mol/l) potentiated the contractions elicited by electrical stimulation and potassium chloride, and produced leftward shifts of the concentration-response curve for noradrenaline. The TXA(2) receptor antagonist SQ-30741 (10(-8) mol/l) prevented the potentiation evoked by U-46619. The dihydropyridine calcium antagonist nifedipine (10(-6) mol/l) did not affect the potentiation of electrical stimulation and noradrenaline induced by U-46619, but abolished the potentiation of U-46619 on KCl-induced contractions., Conclusions: U-46619 facilitates sympathetic neurotransmission and potentiates constrictor effects of noradrenaline in human saphenous veins through stimulation of TXA(2) receptors. These effects are independent of calcium entry through dihydropyridine calcium channels.

Objectives: Plasma levels of endogenous guanidino-substituted analogues of L -arginine are increased in various pathologic conditions. In the present study we determined the effects of some of these compounds on basal and stimulated release of nitric oxide in human internal thoracic and radial arteries., Methods: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for isometric recording of tension., Results: N(G)-monomethyl L -arginine (10(-6) to 10(-3) mol/L) and N(G),N(G)-dimethyl L -arginine (10(-6) to 10(-3) mol/L) caused concentration- and endothelium-dependent contractions. Maximal force of contractions for N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine in the internal thoracic artery were 18.0% +/- 4.3% and 17.8% +/- 3.8%, respectively, of the contraction to 100 mmol/L KCl, and those found in the radial artery were 9.6% +/- 2.5% and 9.1% +/- 2.4%, respectively. Aminoguanidine (10(-5) to 3 x 10(-3) mol/L) and methylguanidine (10(-5) to 3 x 10(-3) mol/L) produced endothelium-independent contractions. L -Arginine (10(-3) mol/L) prevented the contractions by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine but did not change contractions induced by aminoguanidine and methylguanidine. N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine inhibited, in a concentration-dependent manner, the endothelium-dependent relaxation to acetylcholine in the internal thoracic artery and had little attenuating effect in the radial artery; aminoguanidine and methylguanidine were without effect., Conclusions: The results suggest that the contractions induced by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine are due to inhibition of both basal and stimulated nitric oxide production, whereas aminoguanidine and methylguanidine do not affect the synthesis of nitric oxide. An increase in the plasma concentration of N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine is likely to represent a risk factor for abnormal vasomotor tone in conduit arteries used as coronary grafts.

Background: Sildenafil is currently used in the treatment of erectile dysfunction. However, assessment of direct effects of sildenafil on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects of sildenafil on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison., Methods: Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was recorded. Then the effects of sildenafil, zaprinast, and sodium nitroprusside on precontracted vessels were studied., Results: Sildenafil (10(-8) - 3 x 10(-5) mol/L) caused concentration-dependent relaxation in the internal mammary arteries, radial arteries, and forearm veins. In the coronary arteries, sildenafil had a modest relaxant effect. In addition, sildenafil amplified the relaxation induced by sodium nitroprusside in all four vessels. Relaxation was unaffected by the inhibitor of nitric oxide synthase NG-monomethyl-L-arginine (10(-4) mol/L). Compared with zaprinast, sildenafil was eight to ten times more potent in terms of EC50 values., Conclusions: The direct relaxant effects of sildenafil together with its synergistic interaction with nitric oxide donors should be considered in patients undergoing coronary bypass surgery, patients with low blood pressure, and patients receiving antihypertensive regimes.

Objectives: To investigate the effects of sildenafil on human penile blood vessels and evaluate the interaction of sildenafil with neurogenic-mediated responses. Sildenafil is currently used in the treatment of erectile dysfunction., Methods: Penile dorsal arteries and deep dorsal veins were obtained from 14 multiorgan donors. Vascular rings were suspended in organ bath chambers, and the isometric tension was recorded. We then studied the effects of sildenafil on precontracted vessels and the neurogenic (noradrenergic and nitrergic) responses., Results: Sildenafil (10(-9) to 3 x 10(-6) M) caused concentration-dependent relaxation and amplified the relaxation induced by sodium nitroprusside. Relaxation was unaffected by the inhibitor of nitric oxide synthase N(G)-monomethyl-L-arginine (10(-4) M). Compared with zaprinast, sildenafil was 8 to 10 times more potent in terms of the median effective concentration (EC(50)) values. Electrical field stimulation of the vessels under resting tension caused frequency-dependent contractions that were attenuated in the presence of sildenafil. When penile vessels were contracted after blockade of norepinephrine release with guanethidine (10(-6) M), electrical stimulation induced frequency-dependent, nitric oxide-dependent relaxations that were enhanced by sildenafil., Conclusions: These results indicate that the relaxation of human penile arteries and veins induced by sildenafil involves inhibition of noradrenergic contraction, enhancement of neurogenic nitric oxide-mediated relaxation, and inhibition of smooth muscle contraction.

The present study was designed to characterize the response of human penile dorsal artery and deep dorsal vein to dilator drugs used in the diagnosis and treatment of erectile dysfunction with special emphasis on the effects on sympathetic neurotransmission. Ring segments of penile dorsal artery and deep dorsal vein were obtained from 20 multi-organ donors during procurement of organs for transplantation. The rings (3 mm long) were suspended in organ bath chambers for isometric recording of tension. We then studied the relaxant responses to prostaglandin E1 (PGE1), vasoactive intestinal peptide (VIP), papaverine (PV), sodium nitroprusside (SNP) and linsidomine chlorhydrate (SIN-1), and analysed the effects of these drugs on contractions induced by stimulation of perivascular sympathetic nerves. In artery and vein rings contracted by noradrenaline, all the drugs tested caused concentration-dependent relaxation. The order of potencies in terms of IC50 values (concentration of agonist causing 50% of the maximal relaxation) was PGE1=VIP>SNP>SIN-1=PV. Both arteries and veins contracted to electrical field stimulation (15 V, 0.5-2 Hz, 0.2 ms duration for 15 s) in a frequency-dependent manner. All relaxant drugs caused concentration-dependent inhibition of neurogenic contractions; the relative order of potencies was PGE1>VIP>SNP>SIN-1=PV. It is concluded that inhibition of sympathetic activity constitutes an effective relaxing mechanism in penile dorsal artery and vein. Modulation of sympathetic activity together with the direct effects on smooth muscle should be considered to evaluate adequately the efficacy of relaxant drugs to increase human penile blood supply.

We have used in vitro preparations of human penile dorsal artery and deep dorsal vein from 20 multiorgan donors to investigate whether subpressor concentrations of vasopressin facilitate noradrenergic transmission in penile blood vessels. Vasopressin constricted penile dorsal arteries (pD2, 9.38 +/- 0.18) and deep dorsal veins (pD2, 9. 40 +/- 0.14) by activating V1 receptors. Vasopressin (10(-11) and 3 x 10(-11) M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (15 V, 0.5-2 Hz, 0.2 msec duration for 15 sec) and produced leftward shifts of the concentration-response curve for norepinephrine. The V1 receptor antagonist d(CH2)5Tyr(Me)AVP (3 x 10(-9)-10(-7) M) induced concentration-dependent inhibitions of potentiation caused by vasopressin. In contrast, the V2 receptor antagonist [d(CH2)5,D-Ile2, Ile4,Arg8]-vasopressin (10(-8)-10(-7) M) did not prevent the potentiation induced by vasopressin. The results demonstrate that vasopressin exerts powerful constrictor action in human penile arteries and veins by direct stimulation of V1 receptors. In addition, vasopressin strongly potentiates the contractions to norepinephrine and stimulation of perivascular adrenergic nerves. Consequently, the direct contractile effects of vasopressin together with its amplifying effects on adrenergic-mediated constriction should be taken into consideration in the overall regulation of penile erection and in those states characterized by increased plasma vasopressin levels.

1. The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin. 2. Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents. 3. Electrical field stimulation (0.5-2 Hz) and noradrenaline (3 x 10(-10)-3 x 10(-5) M) caused frequency- and concentration-dependent contractions that were of greater magnitude in veins denuded of endothelium. The inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, l0(-4) M) increased the adrenergic responses only in rings with endothelium. 4. In preparations contracted with noradrenaline in the presence of guanethidine (10(-6) M) and atropine (10(-6) M), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NAME, methylene blue (3 x 10(-5) M) and tetrodotoxin (10(-6) M), but was unaffected by removal of endothelium. 5. Acetylcholine (10(-8)-3 x 10(-5) M) and substance P (3 x 10(-11) -3 x 10(-7) M) induced endothelium-dependent relaxations. In contrast, sodium nitroprusside (10(-9)-3 x 10(-5) M) and papaverine (10(-8) 3 x 10(-5) M) caused endothelium-independent relaxations. 6. The results provide functional evidence that the human penile deep dorsal vein is an active component of the penile vascular resistance through the release of nitric oxide from both neural and endothelial origin. Dysfunction in any of these sources of nitric oxide should be considered in some forms of impotence.

Background: Arginine vasopressin (AVP) not only acts directly on blood vessels through V1 receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vivo and in vitro. The aim of the present study was to investigate whether AVP can contribute to an abnormal adrenergic constrictor response of human saphenous veins., Methods and Results: Saphenous vein rings were obtained from 32 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. AVP (3x10[-9] mol/L) enhanced the contractions elicited by electrical field stimulation at 1, 2, and 4 Hz (by 80%, 70%, and 60%, respectively) and produced a leftward shift of the concentration-response curve to norepinephrine (half-maximal effective concentration decreased from 6.87x10[-7] to 1.04x10[-7] mol/L; P<.05). The V1 vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP (10[-6] mol/L) prevented the potentiation evoked by AVP. The selective V1 receptor agonist [Phe,2 Orn8]-vasotocin (3x[-10]-9 mol/L) induced potentiation of electrical stimulation-evoked responses, which was also inhibited in the presence of the V1 receptor antagonist (10[-6] mol/L). In contrast, the V2 receptor agonist desmopressin (10[-9] to 10[-7] mol/L) did not modify neurogenic responses, and the V2 receptor antagonist [d(CH2)5, D-Ile,2 Ile,4 Arg8]-vasopressin (10[-8] to 10[-6] mol/L) did not prevent the potentiation induced by AVP. The dihydropyridine calcium antagonist nifedipine (10[-6] mol/L) did not affect the potentiating effect of AVP., Conclusions: The results suggest that low concentrations of AVP facilitate sympathetic neurotransmission and potentiate constrictor effects of norepinephrine in human saphenous veins. These effects appear to be mediated by V1 receptor stimulation and are independent of calcium entry through dihydropyridine calcium channels. Thus, AVP may contribute to vascular mechanisms involved in acute ischemic syndromes associated with venous grafts, particularly if the sympathetic nervous system is activated.

Purpose: The goal of this study was to determine the effects of vasopressin and the selective V2-receptor agonist desmopressin on human saphenous veins, with special emphasis on endothelium-mediated responses., Methods: Human saphenous vein segments were obtained from 35 patients undergoing coronary bypass surgery. Paired segments, one normal and the other deendothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Concentration-response curves to vasopressin and desmopressin were determined in the presence and in the absence of either the V1-receptor antagonist d(CH2)5Tyr (Me)AVP (10(-6) mol/L), the V1-V2-receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (10(-6) mol/L), indomethacin (10(-6) mol/L), or NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10(-4) mol/L)., Results: In vein rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with a concentration of vasopressin producing half-maximal contractions (EC50) of 3.44 x 10(-8) mol/L. The vasopressin V1-receptor antagonist (10(-6) mol/L) displaced the control curve to vasopressin 9.86-fold to the right in a parallel manner. In precontracted vein rings previously treated with the V1-antagonist (10(-6) mol/L) vasopressin caused endothelium-dependent relaxations. This relaxation was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the V1-V2-receptor antagonist (10(-6) mol/L) or by L-NAME (10(-4) mol/L). Desmopressin caused endothelium-dependent relaxations in precontracted vein rings that were inhibited by the mixed V1-V2-receptor antagonist and by indomethacin, but not by the V1-antagonist or by pretreatment with L-NAME., Conclusions: These observations indicate that vasopressin exerts contractile effects on human saphenous vein by V1-receptor stimulation. Vasopressin causes dilatation of human saphenous vein only if V1-receptor blockade is present. This relaxation appears to be mediated by the release of relaxant prostaglandins, probably derived from endothelial cells, and is independent of V2-receptor stimulation or release of nitric oxide. Desmopressin elicits relaxation that is largely dependent on V2-receptor stimulation, which may bring about the release of dilating prostaglandins from the endothelial cells.