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Summary: Exercise capacity as well as many resting central and peripheral haemodynamic features declines by age. We aimed to investigate which haemodynamic features change the most during life and which change in parallel to exercise capacity. We performed a maximal bicycle exercise test with gas exchange in 103 healthy subjects (24 young, 55 middle‐aged and 24 elderly). Endothelial function, arterial compliance/stiffness and heart rate variability (HRV) were evaluated, and the myocardium and carotid arteries were investigated by ultrasound. Exercise capacity declined by almost 50% over the lifespan. Several markers reflecting arterial compliance/stiffness and HRV, as well as carotid intima–media thickness (IMT), showed lifetime impairments by >100%, while markers of LV systolic function, diastolic blood pressure and carotid artery blood flow showed only minor changes with age. The decline in exercise capacity clusters closely with many other variables measured during the exercise test, but also to resting vital capacity, left ventricular end‐diastolic diameter and resting gas exchange (VO2, VCO2) to a lesser degree. Resting vital capacity was closely related to exercise capacity in the middle‐aged group. We conclude that many of the resting markers of central and peripheral haemodynamics declined during life, in parallel to the decline in exercise capacity. However, some haemodynamic features, such as LF/HF ratio at HRV, stiffness index beta of the carotid artery, and heart rate reserve at the exercise test, showed a more exaggerated decline, indicating that those are not closely linked to exercise capacity. [ABSTRACT FROM AUTHOR]

Abstract: Endothelial dysfunction is known to be the early stage of arteriosclerosis. The flow‐mediated dilation (FMD) test is the most commonly used method to diagnose the endothelial function. The test measures the maximum vasodilation (FMD response) on the brachial artery induced by the increases in blood flow after cuff deflation on the forearm. The vessel diameter must be captured clearly with the ultrasonic probe during the test. The vasodilation is induced in response to changes in the mechanical property of the vessel wall due to the blood flow stimulation. The changes are supposed to affect the pulsatile flow, but the influence of continuous behavior of vascular property on hemodynamics has not been clarified. In this study, in order to clarify the influence of the FMD response on hemodynamics, we propose a mathematical model that can simulate hemodynamics and vasomotor responses. As a result, it was shown that vessel wall dynamics affected the pulsatile flow. This result suggests that the endothelial function can be evaluated from blood flow. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle contraction and the myogenic response regulate blood flow in the resistance vascular and contribute to systemic blood pressure. Three pathways are currently known to contribute to the development of the myogenic response: (i) Ca2+-dependent phosphorylation of LC20; (ii) Ca2+ sensitization through inhibition of myosin phosphatase; and (iii) cortical actin polymerization. A number of regulatory smooth muscle proteins are integrated with these pathways to fine tune the response and facilitate adaptations to vascular (patho)physiologies. Of particular interest is the SMTN family of proteins, consisting of SMTN-A, SMTN-B, and the SMTN-like protein, SMTNL1. The SMTN-B and SMTNL1 proteins are both implicated in regulating smooth muscle contractility and contributing to vascular adaptations associated with hypertension, pregnancy, and exercise training. In the case of SMTNL1, the protein plays multiple roles in regulating contraction through functional interactions with contractile regulators as well as transcriptional control of the contractile phenotype and Ca2+-sensitizing capacity. For the first time, preliminary results suggest SMTNL1 is involved in the myogenic response of the cerebral resistance vasculature. In this regard, global SMTNL1 deletion is associated with greater myogenic reactivity of cerebral arterioles, although the precise mechanism accounting for this finding remains to be defined. [ABSTRACT FROM AUTHOR]

Herein, we review mechanisms regulating cerebral blood flow (CBF), with specific focus on humans. We revisit important concepts from the older literature and describe the interaction of various mechanisms of cerebrovascular control. We amalgamate this broad scope of information into a brief review, rather than detailing any one mechanism or area of research. The relationship between regulatory mechanisms is emphasized, but the following three broad categories of control are explicated: (1) the effect of blood gases and neuronal metabolism on CBF; (2) buffering of CBF with changes in blood pressure, termed cerebral autoregulation; and (3) the role of the autonomic nervous system in CBF regulation. With respect to these control mechanisms, we provide evidence against several canonized paradigms of CBF control. Specifically, we corroborate the following four key theses: (1) that cerebral autoregulation does not maintain constant perfusion through a mean arterial pressure range of 60-150 mmHg; (2) that there is important stimulatory synergism and regulatory interdependence of arterial blood gases and blood pressure on CBF regulation; (3) that cerebral autoregulation and cerebrovascular sensitivity to changes in arterial blood gases are not modulated solely at the pial arterioles; and (4) that neurogenic control of the cerebral vasculature is an important player in autoregulatory function and, crucially, acts to buffer surges in perfusion pressure. Finally, we summarize the state of our knowledge with respect to these areas, outline important gaps in the literature and suggest avenues for future research. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine (i) the cardiovascular responses to acute blood-flow-restricted ( BFR) resistance exercise and (ii) the influence of applied BFR cuff type on the cardiovascular and perceptual responses. Methods In a randomized, crossover design, 27 participants wore either a 5·0 cm wide elastic cuff or a 13·5 cm wide non-elastic cuff around the thigh while performing four sets of knee extension exercise using 20% of 1- RM. Brachial and central blood pressure ( BP) and aortic augmentation index ( AIx) were measured before and after the restrictive cuffs were applied and inflated, after the 2nd and 4th set of resistance exercise, and 5 and 15 min following the 4th set of exercise. Ratings of perceived exertion and pain were obtained before exercise and after the 2nd and 4th set of exercise. Results Both brachial and central BPs increased and AIx decreased during BFR exercise but returned to baseline levels within 15 min following exercise. The wide cuffs caused a greater elevation in heart rate, brachial and central BPs, perceived effort and pain and a greater decrease in AIx during the BFR exercise. Conclusions These findings suggest that low-intensity BFR resistance exercise does not appear to acutely negatively affect the vasculature. Also, cuff type will greatly affect cardiovascular and perceptual responses to BFR resistance exercise and thus is an important consideration in study design. [ABSTRACT FROM AUTHOR]

Two mechanisms control brain blood flow by changing blood vessel diameter: autoregulation maintains flow in the face of perfusion pressure changes, and brain metabolism adjusts flow to meet metabolic requirements. Brain blood vessel reactivity to CO and O is an important component of the latter. We used a specialised rebreathing technique to change CO over a wide range at constant O, estimating brain blood flow responses from measurements of middle cerebral artery flow velocity. We found that below a threshold CO, blood pressure was unchanged, but blood flow increased in response to CO. This response had a sigmoidal shape, centred at a CO close to resting. Above the threshold, both blood flow and pressure increased with CO. We concluded that this method measures the brain blood flow reactivity to CO without the confounding influence of blood pressure changes. The results obtained contribute to our understanding of brain blood flow regulation. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • In vitro studies have shown that urotensin II is a potent arterial vasoconstrictor. • Previous studies investigating the in vivo cardiovascular actions of intra-arterial administration of urotensin II in humans have provided conflicting results. • The cardiovascular actions of intra-arterial administration of the urotensin II receptor antagonist, urantide, are unknown. WHAT THIS STUDY ADDS • We have shown no in vivo effect of urotensin II or urantide on human forearm resistance vessels. • Previous study discrepancies do not seem to relate to either the age or cardiovascular disease (CVD) status of subjects. AIMS (i) To compare the effects of intra-arterial administration of urotensin II in patients with CVD with healthy volunteers, and (ii) to study the haemodynamic effects of intra-arterial infusion of the urotensin II receptor antagonist, urantide. METHODS Ten healthy volunteers and 10 patients with CVD received a dose-ramped brachial artery infusion of urotensin II. A further six healthy male volunteers received a prolonged urotensin II infusion and 11 healthy male volunteers received a dose-ramped infusion of urantide. Forearm blood flow (FBF) was measured every 20 min and blood pressure and heart rate were assessed every 20 min. RESULTS In healthy volunteers and patients with CVD, intra-arterial infusion of urotensin II had no effect on FBF ratio. A dose-ramped infusion of urantide similarly had no effect on FBF ratio. During dose-ramped infusions of urotensin II and urantide, systolic and mean arterial blood pressure increased significantly. In healthy volunteers, urotensin II and urantide, respectively, increased systolic blood pressure from 133 ± 6 to 137 ± 5 mmHg ( P < 0.01) and from 113 ± 4 to 120 ± 4 mmHg ( P < 0.01). In patients with CVD, heart rate also significantly increased during dose-ramped infusion of urotensin II from 59 ± 3 to 62 ± 4 bpm ( P < 0.05). CONCLUSIONS We have shown no in vivo effect of urotensin II or urantide on human forearm resistance vessels. Previous discrepancies do not seem to relate to either the age or CVD status of subjects. Changes in systemic cardiovascular haemodynamics during the dose-ramped infusion studies are unlikely to be caused by urotensin II receptor modulation. [ABSTRACT FROM AUTHOR]

Vaginal vascular responses to vibratory stimulation of the clitoris, recorded as changes in the amplitude of oscillations of light reflectance at the heart-beat frequency, are: a) very repeatable, b) widespread throughout the vagina but of greater amplitude in its lower anterior wall than elsewhere, c) of very short latency (2-3 sec), but cumulative over 30 sec or more. Such responses are not imitated by raising the abdominal pressure, voluntarily contracting the pelvic floor or the flexors or adductors of the hips, or raising the blood pressure by exercise. They are absent in the foot, hand and rectum when present in the vagina. Sexual fantasy provokes vaginal responses very similar to those from vibratory stimulation of the clitoris, though somewhat less repeatable. Mean vaginal light reflectance, averaged over a cardiac cycle, responds to the same stimuli which affect the amplitude of pulsation. It is, however, much more subject to artifact. Changes in thermal conductivity closely parallel those in amplitude of oscillation of reflectance, with a time-lag which is probably mainly instrumental. Vibratory stimulation of the clitoris causes sustained reflex contraction of the pelvic floor. This reflex (never, it seems, previously described) may be regarded as a tonic counterpart of the well-known phasic bulbocavernosus reflex. The vascular events at and after orgasm and their relationship to features of the pelvic floor electromyogram are described and illustrated; the heart rate falls greatly during the 10 sec after orgasm, the amplitude of vaginal vascular pulsation remains above its prestimulation value for as long as 15 mm, and pelvic floor electromyographic activity remains enhanced for at least 2 min. [ABSTRACT FROM AUTHOR]

Collecting lymphatics exhibit spontaneous contractions that are exquisitely sensitive to pressure/flow. The activity of these series-coupled segments propels lymph centrally and serves as an important mechanism to counteract edema. Previously, the pumping behavior of rat mesenteric lymphatics was examined in vivo using cardiac pump indices to analyze adaptations to systemic volume expansion. To quantify this behavior under conditions where input/output pressures and flow could be better controlled, we studied similar vessels after isolation and cannulation in vitro. Segments 2-3 mm in length and ∼100 µm in diameter were viewed at ∼600x using an inverted microscope and diameter tracking system. Pressures at the tips of the inflow and outflow cannulae were controlled independently using a servo system. Pressure in the inter-valve segment was measured with a servo-null pipette. Dynamic changes in the pressure (P)-volume (V) loops representing single contraction cycles were analyzed in response to abrupt (20 ms) steps in afterload and/or preload. Increases in preload led to horizontal expansion of the loop and curvilinear increases in end diastolic V. Increases in afterload expanded the loop vertically; at P>6 cmH2O it collapsed and end systolic V increased. This system can be used to dissect the interaction of intrinsic and extrinsic factors controlling lymphatic contractility. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Exercise mediated increases in sympathetic activity leads to increased production of the non-adrenergic vasoconstrictor Angiotensin II (Angll). PURPOSE: To test the hypothesis that as exercise intensity increases Angll plays a greater role in the control of the peripheral vasculature. METHODS: We compared the vasoconstrictor responses before and after blockade of the Angiotensin type 1 receptor (ATI) with Valsartan (80mg) in healthy humans (n=5) during rest and knee-extensor exercise at ∼40%, 60% and 80% of workmax. Neck suction (NS) stimuli were used to partially withdraw the arterial baroreflex mediated sympathetic activity. Ultrasound Doppler provided measurements of femoral blood flow (FBF) and blood pressures were used to calculate femoral vascular conductance (FVC). RESULTS: FVC was unchanged at rest and during the 40% and 60% exercise trials with Valsartan, however during 80% exercise with Valsartan FVC was increased by 17 ± 3% with Valsartan when compared to control exercise. NS elicited significant increases in FVC during rest and all 3 exercise trials. During 80% exercise NS mediated increases in FVC was further increased by 40 ± 7% with Valsartan when compared to control exercise. CONCLUSION: These data identify that as exercise intensity and duration increases Angll plays a greater percentage role in the control of the peripheral vasculature. [ABSTRACT FROM AUTHOR]

Normoxic hypercapnia increases sympathetic outflow to muscle, presumably causing vasoconstriction. Whether similar responses occur in the cutaneous vasculature is unknown. This study tested the hypothesis that normoxic hypercapnia decreases cutaneous vascular conductance (CVC) during normothermia (NT) and whole-body heating (WBH), with greater reductions in CVC during WBH. Four men and 3 women (mean±SD; age: 34±7 yr) rested supine while wearing a tube-lined suit perfused with 34 °C water (NT), followed by perfusion of 50 °C water to increase internal temperature ∼1 °C (WBH). During each thermal condition, a normoxic 5% CO2 gas mixture was inspired for ∼4 min while forearm skin blood flow (SkBF; laser Doppler flowmetry) and mean arterial blood pressure (MAP) were measured continuously for the subsequent calculation of CVC (SkBF/MAP). End-tidal CO2 increased similarly during hypercapnic exposure in both NT and WBH (+7.9±2.4 and +8.3±1.9 mmHg, respectively; P=0.66). No differences in CVC were observed between pre-hypercapnic baseline and hypercapnia in either NT (P=0.33) or WBH (P=0.87). These results indicate that CVC is not affected by hypercapnia under normothermic and heat stress conditions. Mild hypercapnia, therefore, is unlikely to impair human thermoregulation by means of reducing SkBF. [ABSTRACT FROM AUTHOR]

Vascular sympathetic innervation is a determinant of blood pressure and flow. Its development and maintenance are not well understood. This study tests the hypothesis that semaphorin 3A (Sema3A) and vascular endothelial growth factor (VEGF) interact to modulate axon growth at sympathetic neurovascular junctions. Sema3A induced growth cone collapse (%; mean±se) that was blocked by VEGF. Sema-induced collapse in the absence of VEGF (66±3) was greater than in the presence of VEGF (45±2). VEGF also inhibited Sema3A in neurons grown in the presence of vascular smooth muscle (VSM). VSM inhibited Sema3A; collapse in the presence of VSM (29±2) was less than that in the absence of VSM (44±7). In the absence of vascular-derived VEGF (+ VEGF antibody), VSM no longer inhibited sema3A; collapse in the presence of VSM (37±7) was not different from that in the absence of VSM (39±5). VEGF in neurovascular cultures also increased growth cone area (µm²) and this increase was mediated by VEGFR1. Growth cones in neurovascular cultures grown in the presence of VEGFR1 antibody (57±5) were smaller than in neurovascular cultures grown in the presence of a control antibody (116±11). These data suggest novel interactions between VEGF and sympathetic neurons that may modulate the actions of Sema3A at sympathetic neurovascular junctions and contribute to the development and/or maintenance of vascular sympathetic innervation. [ABSTRACT FROM AUTHOR]

Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor, which also stimulates insulin release. The aim of the present study was to evaluate if exogenously administered ET-1 affected pancreatic islet blood flow in vivo in rats and the islet arteriolar reactivity in vitro in mice. Furthermore, we aimed to determine the ET-receptor subtype that was involved in such responses. When applying a microsphere technique for measurements of islet blood perfusion in vivo ET-1 (5 nmol/kg) consistently and markedly decreased both total pancreatic and especially islet blood flow, despite having only minor effects on blood pressure. Neither endothelin-A (ETA) receptor (BQ-123) nor endothelin-B (ETB) receptor (BQ-788) antagonists, alone or in combination, could prevent this blood flow decrease. To avoid confounding interactions in vivo, we also examined the arteriolar vascular reactivity in isolated, perfused mouse islets. In the latter preparation we demonstrated a dose-dependent constriction in response to ET-1. Administration of BQ-123 prevented this, whereas BQ-788 induced a right-shift in the response. In conclusion, the pancreatic islet vasculature is highly sensitive to exogenous ET-1, which mediates its effect mainly through ETA-receptors, but also ETB-receptors are involved. [ABSTRACT FROM AUTHOR]