Local Vasodilation Research Articles

Physiological changes in energy healers during self-practice

The physiological status of energy healers during self-practice (activating the healing state without the presence of a recipient) has rarely been examined. This study assessed self practice-related changes in autonomic nervous system (ANS) activity in Reiki Masters and advanced Reconnective Healers. Measurements of heart rate (HR), heart rate variability (HRV) and cutaneous blood perfusion of the fingers, of 31 Reiki masters and 50 experienced Reconnective Healers were made before, during and after self-practice. Corresponding measurements were made on 32 control subjects, who gazed at a calming picture in place of self-practice. Experiments were conducted in a laboratory setting. During self-practice by Reconnective Healers, the average HR did not change significantly compared to control subjects but the average HRV and the root mean square of successive differences in inter-beat interval (RMSSD) decreased by 11ms (95% CI 0.6, 4.6, p=0.009) and 13ms (95% CI 0.2, 4.1, p=0.031) more than in control subjects, respectively, indicating reduced parasympathetic nervous activity. Reiki Masters showed no significant change in HR, HRV or RMSSD compared to control subjects. Cutaneous blood perfusion increased during self-practice relative to control subjects in both Reconnective Healers (6.5%; p=0.012) and Reiki Masters (13.7%; p<0.001). Contrary to expectations, neither Reconnective Healers nor Reiki practitioners appear to enter a more physiologically relaxed state during self-practice although there is a local peripheral vasodilatation that is probably mediated by humoral agents.

Acute Mesenteric Ischemia

Acute mesenteric ischemia is still fatal in 50% to 70% of cases. This consensus paper was written with the participation of physicians from all of the involved specialties for the purpose of improving outcomes. Mesenteric ischemia must be recognized as a vascular emergency requiring rapid and efficient clinical evaluation and treatment. We reviewed pertinent literature that was retrieved by a PubMed search on the terms "mesenteric ischemia" AND "arterial" OR "venous" OR "clinical presentation" OR "diagnosis" OR "therapy" OR "surgery" OR " interventional radiology." Our review also took account of the existing guidelines of the American College of Cardiology/American Heart Association. Intensive discussions among the participating physicians, representing all of the specialties involved in the management of mesenteric ischemia, led to the creation of this interdisciplinary paper. Biphasic contrast-enhanced computerized tomography is the diagnostic tool of choice for the detection of arterial or venous occlusion. If non-occlusive mesenteric ischemia is suspected, angiography should be performed, with the option of intraarterial pharmacotherapy to induce local vasodilation. Endovascular techniques have become increasingly important in the treatment of arterial occlusion. Embolic central mesenteric artery occlusion requires surgical treatment; surgery is also needed in case of peritonitis. Portal-vein thrombosis can be treated by local thrombolysis through a transhepatically placed catheter. This should be done within 3 to 4 weeks of the event to prevent later complications of portal hypertension. Rapid diagnosis (within 4 to 6 hours of symptom onset) and interdisciplinary cooperation in the provision of treatment are required if the poor outcome of this condition is to be improved.

Ankle position modifies tibialis anterior muscle perfusion and oxygenation in the human leg

Near‐infrared spectroscopy (NIRS) is a noninvasive technique used to monitor muscle oxygenation. Photoplethysmography (PPG) is a noninvasive measure of muscle microvascular blood flow. NIRS and PPG were used in seven tibialis anterior (TA) muscles of five healthy volunteers (3 male, 2 female) aged 31.2±7.8 years (mean, SD) in order to determine whether oxygenation and blood flow of the TA varied with ankle position. Data from the resting ankle position (mean of 11.5º plantarflexion) were compared to following test positions: full passive plantarflexion (PF), passive neutral (Neu) or 0º, and full passive dorsiflexion (DF). Mean oxygenation of the TA muscle yielded significant decreases for PF (p&lt;0.01) and DF (p&lt;0.01), but no significant difference for Neu (p=0.10). Mean perfusion of the TA muscle increased significantly for PF (p=0.027), Neu (p=0.012), and DF (p=0.010). Based on prior research, it was expected that oxygenation levels would decrease across the test ankle positions; however, it was not anticipated that perfusion would increase. Our novel results suggest that local compensatory vasodilation within muscle exists in order to increase microvascular blood flow under conditions of relative tissue hypoxia. These findings are important to the understanding of the local hemodynamic response in the human leg in relation to changes in ankle position from rest.

Adenosine and NO blockade decreases skeletal muscle interstitial pH during hypoxia

The present study examined the effects that blocking local adenosine and nitric oxide production has on skeletal muscle interstitial pH and H+ during hypoxia. Eight anesthetized rats had two microdialysis fibers inserted into the gastrocnemius muscle of each leg and perfused with Ringers (control) or 500 μM AOPCP (5′ectonucleotidase inhibitor) plus 10 mM L‐NAME (NOS inhibitor). Following baseline collections (20 min with saline, Baseline 1), all the probes were perfused with the both blockers for (20 min, Baseline 2) followed by 20 min of hypoxia (inhalation of 10.5% O2) and recovery. The perfusion of the blockers resulted in a decrease (P&lt;0.05) in skeletal muscle interstitial pH and a reciprocal increase (P&lt;0.05) in interstitial H+during normoxia (Baseline 2) and these changes were further exaggerated during hypoxia as well as recovery (Figures)1. These data clearly demonstrate that blocking local vasodilators most likely resulted in a decrease in local tissue blood flow and an accumulation of H+, which is further elevated under anaerobic conditions such as hypoxia.

ATP‐mediated vasodilation occurs via vascular hyperpolarization in humans

ATP possesses unique vasomotor properties and has been hypothesized to contribute to the control of vascular tone under a variety of physiological conditions; however, in humans, the underlying vasomotor signaling mechanisms remain unknown. We sought to determine whether ATP‐mediated vasodilation occurs via vascular hyperpolarization in young healthy humans. In Protocol 1 (n=8), progressive doses of ATP and potassium chloride (KCl) were infused via brachial artery catheter. Forearm vascular conductance (FVC) was calculated from forearm blood flow (venous occlusion plethysmography) and intra‐arterial blood pressure to quantify local vasodilation. Vasodilatory responses (%ΔFVC) to ATP infusions were unchanged following combined inhibition of nitric oxide (NO) and prostaglandins (PGs; P&gt;0.05) whereas the response to KCl was significantly greater (P&lt;0.05). In Protocol 2 (n=21), infusion of both ouabain (to inhibit Na+/K+ ATPase) and barium chloride (BaCl2; to inhibit KIR channels) abolished KCl‐mediated vasodilation (%ΔFVC= 134±13 vs 4±5%; P&lt;0.05) indicating effective inhibition of vasodilation mediated via hyperpolarization. On average, forearm vasodilation to 3 doses of ATP was inhibited ~60% following combined ouabain+BaCl2 infusion. Our novel results indicate that the majority of vasodilation in response to ATP occurs via vascular hyperpolarization in humans. Supported by HL102720

Serotonin and CGRP in migraine.

Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied by gastrointestinal and visual disorders. Migraine is more prevalent in females than males with a ratio of 3:1. It is primarily a complex neurovascular disorder involving local vasodilation of intracranial, extracerebral blood vessels and simultaneous stimulation of surrounding trigeminal sensory nervous pain pathway that results in headache. The activation of 'trigeminovascular system' causes release of various vasodilators, especially calcitonin gene-related peptide (CGRP) that induces pain response. At the same time, decreased levels of neurotransmitter, serotonin have been observed in migraineurs. Serotonin receptors have been found on the trigeminal nerve and cranial vessels and their agonists especially triptans prove effective in migraine treatment. It has been found that triptans act on trigeminovascular system and bring the elevated serum levels of key molecules like calcitonin gene related peptide (CGRP) to normal. Currently CGRP receptor antagonists, olcegepant and telcagepant are under consideration for antimigraine therapeutics. It has been observed that varying levels of ovarian hormones especially estrogen influence serotonin neurotransmission system and CGRP levels making women more predisposed to migraine attacks. This review provides comprehensive information about the role of serotonin and CGRP in migraine, specifically the menstrual migraine.

Imaging of muscle blood volume changes during exercise with Vascular Space Occupancy (VASO) MRI

Large, rapid changes in perfusion accompany exercise, mediated in part by a local vasodilatory response. Impaired vasodilation occurs in diabetes, obesity, and other conditions. VASO MRI was developed to measure blood volume changes in the brain by nulling the signal of blood; vasodilation thus causes a loss of MRI signal intensity. The purpose of this work was to implement VASO for skeletal muscle. Eighteen subjects participated in the optimization of this method. Subjects were placed supine in a Philips 3.0T scanner with their foot on a force transducer, a knee coil around the calf, and an occlusion cuff around the thigh. Anatomical and VASO images were acquired (Fig 1).Maximal plantarflexion contractions were performed for 1–20 seconds, six minutes apart. The cuff was inflated to 240 mm Hg for five minutes, occluding arterial flow; VASO response was monitored for up to fifteen minutes after cuff release. NIRS spectroscopy was also performed to relate observed VASO signal changes to blood oxygenation and volume changes. VASO signal follows a similar time course to NIRS post occlusion.The decrease in VASO signal following a series of three ten second maximal plantarflexion contractions, as shown in Fig 2, should be proportional to increased blood volume demonstrating the promise of this new imaging paradigm to study blood volume changes in exercising muscle. This work was supported by NIH/NIAMS R01 AR050101.

Acute feedback control of astrocytic glycolysis by lactate

Neuronal activity is accompanied by a rapid increase in interstitial lactate, which is hypothesized to serve as a fuel for neurons and a signal for local vasodilation. Using FRET microscopy, we report here that the rate of glycolysis in cultured mice astrocytes can be acutely modulated by physiological changes in extracellular lactate. Glycolytic inhibition by lactate was not accompanied by detectable variations in intracellular pH or intracellular ATP and was not dependent of mitochondrial function. Pyruvate was also inhibitory, suggesting that the effect of lactate is not mediated by the NADH/NAD(+) ratio. We propose that lactate serves as a fast negative feedback signal limiting its own production by astrocytes and therefore the amplitude of the lactate surge. The inhibition of glucose usage by lactate was much stronger in resting astrocytes than in K(+)-stimulated astrocytes, which suggests that lactate may also help diverting glucose from resting to active zones.

Intrastriatal convection-enhanced delivery results in widespread perivascular distribution in a pre-clinical model

BackgroundConvection-enhanced delivery (CED), a direct method for drug delivery to the brain through intraparenchymal microcatheters, is a promising strategy for intracerebral pharmacological therapy. By establishing a pressure gradient at the tip of the catheter, drugs can be delivered in uniform concentration throughout a large volume of interstitial fluid. However, the variables affecting perivascular distribution of drugs delivered by CED are not fully understood. The aim of this study was to determine whether the perivascular distribution of solutes delivered by CED into the striatum of rats is affected by the molecular weight of the infused agent, by co-infusion of vasodilator, alteration of infusion rates or use of a ramping regime. We also wanted to make a preliminary comparison of the distribution of solutes with that of nanoparticles.MethodsWe analysed the perivascular distribution of 4, 10, 20, 70, 150 kDa fluorescein-labelled dextran and fluorescent nanoparticles at 10 min and 3 h following CED into rat striatum. We investigated the effect of local vasodilatation, slow infusion rates and ramping on the perivascular distribution of solutes. Co-localisation with perivascular basement membranes and vascular endothelial cells was identified by immunohistochemistry. The uptake of infusates by perivascular macrophages was quantified using stereological methods.ResultsWidespread perivascular distribution and macrophage uptake of fluorescein-labelled dextran was visible 10 min after cessation of CED irrespective of molecular weight. However, a significantly higher proportion of perivascular macrophages had taken up 4, 10 and 20 kDa fluorescein-labelled dextran than 150 kDa dextran (p < 0.05, ANOVA). Co-infusion with vasodilator, slow infusion rates and use of a ramping regime did not alter the perivascular distribution. CED of fluorescent nanoparticles indicated that particles co-localise with perivascular basement membranes throughout the striatum but, unlike soluble dextrans, are not taken up by perivascular macrophages after 3 h.ConclusionsThis study suggests that widespread perivascular distribution and interaction with perivascular macrophages is likely to be an inevitable consequence of CED of solutes. The potential consequences of perivascular distribution of therapeutic agents, and in particular cytotoxic chemotherapies, delivered by CED must be carefully considered to ensure safe and effective translation to clinical trials.

Application of Local Anesthesia Inhibits Effects of Low-Energy Extracorporeal Shock Wave Treatment (ESWT) on Nociceptors

Clinical studies of extracorporeal shock wave therapy (ESWT) provided conflicting results depending on the use of local anesthesia (LA). The present study investigated whether the biological effects of ESWT differ between application with and without LA. In 20 healthy subjects, ESWT was applied to the ventral surface of forearm skin, either after topical lidocaine pretreatment or without on the corresponding contralateral side. During and after ESWT ongoing pain, axon-reflex vasodilation (laser Doppler imaging), thresholds for pinprick, and blunt pressure were recorded. The results indicate that increasing ESWT energy flux density led to increasing pain (P < 0.001). LA reduced ESWT-related pain (P < 0.02) and in parallel inhibited local axon-reflex vasodilation (P < 0.001). In addition, LA prevented ESWT-related drop in pressure pain threshold (P < 0.001). This study provided evidence that ESWT dose-dependently activates and sensitizes primary afferent nociceptive C-fibers, and that both activation and sensitization were prevented if LA was applied locally. These results suggest that LA substantially alters the biological responses of ESWT.

TRP-channel-specific cutaneous eicosanoid release patterns

Analyzing mechanisms and key players in peripheral nociception nonneuronal skin cells are getting more and more into focus. Herein we investigated the functional expression of TRPV1 and TRPA1 in human keratinocytes and fibroblasts and assessed proinflammatory lipid mediator release upon their stimulation as well as sensory effects after topical application, combining in vitro and in vivo approaches. In vitro, the expression of functional TRPV1 and TRPA1 channels on fibroblasts and keratinocytes was confirmed via immunofluorescence, qualitative real time (RT) polymerase chain reaction, and cellular Ca 2+ influx measurements. Additionally, the agonists allyl isothiocyanate (TRPA1) and capsaicin (TRPV1) induce a differential secretion pattern of the eicosanoids PGE 2 and LTB 4 in human dermal fibroblasts and keratinocytes, which was also detectable in vivo, analyzing suction blister fluid at various times after short-term topical application. Capsaicin provoked the release of LTB 4 at 2 and 24 hours. In contrast, PGE 2 levels were reduced upon stimulation. Allyl isothiocyanate, however, increased PGE 2 levels only at 24 hours, but did not alter LTB 4 levels. In parallel, heat pain thresholds were reduced by both agents after short-term topical application, but only AITC provoked a long-lasting local erythema. In conclusion, the agonist-induced activation of nociceptors by TRPA1 and TRPV1 elicits painful sensations, whereas nonneuronal tissue cells respond with differential release of inflammatory mediators, thus influencing local vasodilatation and neuronal sensitization. These results have implications for the application of transient receptor potential antagonists to improve inflammatory skin conditions and pain management.

Ranolazine Injection Into Coronary or Femoral Arteries Exerts Marked, Transient Regional Vasodilation Without Systemic Hypotension in an Intact Porcine Model

We examined whether intracoronary or intrafemoral administration of ranolazine produces local vasodilation. Effects of intra-arterial ranolazine on coronary and femoral artery vasodilation and systemic hemodynamic function were studied in anesthetized pigs (n=27). Ranolazine, nitroglycerin, or saline (control) was injected into the left anterior descending (LAD) coronary artery or femoral artery (2-mL bolus in 10 seconds). Pretreatment with prazosin (300 μg/kg IV) allowed determination of α(1)-adrenergic receptor involvement (n=8). Rapid intracoronary administration of ranolazine (0.048 mg/kg) to achieve high local concentrations resulted in 91±11% increase in LAD coronary artery flow and 39±7% reduction in coronary vascular resistance (both, P<0.0001). This effect lasted 2-3 minutes without change in heart rate or rate-pressure product. Mean arterial pressure decreased marginally (by 2±1 mm Hg, P=0.01). Maximum systemic plasma concentration (0.93±0.29 μmol/L) remained in subtherapeutic range. Pretreatment with prazosin abolished these effects. Intracoronary nitroglycerin (100 μg) increased LAD coronary artery flow by 112±25% (P=0.02), but the effect lasted <2 minutes; mean arterial pressure decreased by 4±1 mm Hg (P=0.01). Intrafemoral injection of ranolazine (0.24 mg/kg, ie, one-tenth of the systemic bolus) resulted in a 70±19% increase in femoral artery flow (P=0.05) and 26±5% reduction in femoral artery resistance (P=0.004). At 2 minutes after the injection, the femoral flow remained 16±9% above the baseline and dilatory effects occurred without tolerance to repeated injections. Intracoronary or intrafemoral ranolazine bolus exerts a marked, 2- to 3-minute dilatory effect that is comparable to nitroglycerin in magnitude but more persistent, attributable primarily to α(1)-adrenergic blockade.

Dietary Nitrite in Nitric Oxide Biology: A Redox Interplay with Implications for Pathophysiology and Therapeutics

Until recently, nitrite has been considered a stable oxidation inert metabolite of nitric oxide ((∙)NO) metabolism. This view is now changing as it has been shown that nitrite can be reduced back to (∙)NO and thus one may consider a reversible interaction regarding (∙)NO:nitrite couple. Not only physiological regulatory actions have been assigned to nitrite but also may represent, in addition to nitrate, the largest (∙)NO reservoir in the body. This notion has obvious importance when considering that (∙)NO is a ubiquitous regulator of cell functions, ranging from neuromodulation to the regulation of vascular tone. Particularly in the stomach, following ingestion of nitrate and food or beverages-containing polyphenols, a rich chemistry occurs in which (∙)NO, (∙)NO-derived species and nitroso or nitrated derivatives may be formed. Most of these molecules may play an important role in vivo. For instance, it has been shown that polyphenol-catalyzed nitrite reduction to (∙)NO may induce local vasodilation and that ethanol (from wine) reacts with (∙)NO-derived species yielding nitroso derivatives endowed with (∙)NO-donating properties. Thus, this review reveals new pathways for the biological effects of dietary nitrite encompassing its interaction with dietary components (polyphenols, red wine, lipids), yielding products with impact on human physiology and pathology, namely cardiovascular, urinary and gastrointestinal systems. Novel therapeutic strategies are therefore expected to follow the elucidation of the mechanisms of nitrite biology.

Augmented skeletal muscle hyperaemia during hypoxic exercise in humans is blunted by combined inhibition of nitric oxide and vasodilating prostaglandins

Exercise hyperaemia in hypoxia is augmented relative to the same level of exercise in normoxia. At moderate exercise intensities, the mechanism(s) underlying this augmented response are currently unclear. We tested the hypothesis that endothelium-derived nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute to the augmented muscle blood flow during hypoxic exercise relative to normoxia. In 10 young healthy adults, we measured forearm blood flow (FBF; Doppler ultrasound) and calculated the vascular conductance (FVC) responses during 5 min of rhythmic handgrip exercise at 20% maximal voluntary contraction in normoxia (NormEx) and isocapnic hypoxia (HypEx; O2 saturation ∼85%) before and after local intra-brachial combined blockade of NO synthase (NOS; via N(G)-monomethyl-L-arginine: L-NMMA) and cyclooxygenase (COX; via ketorolac). All trials were performed during local α- and β-adrenoceptor blockade to eliminate sympathoadrenal influences on vascular tone and thus isolate local vasodilatation. Arterial and deep venous blood gases were measured and oxygen consumption (VO2) was calculated. In control (saline) conditions, FBF after 5 min of exercise in hypoxia was greater than in normoxia (345 ± 21 ml min(−1) vs. 297 ± 18 ml min(−1); P < 0.05). After NO–PG block, the compensatory increase in FBF during hypoxic exercise was blunted ∼50% and thus was reduced compared with control hypoxic exercise (312 ± 19 ml min(−1); P < 0.05), but this was not the case in normoxia (289 ± 15 ml min(−1); P = 0.33). The lower FBF during hypoxic exercise was associated with a compensatory increase in O2 extraction, and thus VO2 was maintained at normal control levels (P = 0.64–0.99). We conclude that under the experimental conditions employed, NO and PGs have little role in normoxic exercise hyperaemia whereas combined NO–PG inhibition reduces hypoxic exercise hyperaemia and abolishes hypoxic vasodilatation at rest. Additionally, VO2 of the tissue was maintained in hypoxic conditions at rest and during exercise, despite attenuated oxygen delivery following NO–PG blockade, due to an increase in O2 extraction at the level of the muscle.

Local action for global vision

Local action for global vision

The role of nitrite in neurovascular coupling

Nitric oxide (NO), a potent vasodilator and nontraditional neurotransmitter, is an important mediator of the changes in cerebral blood flow (CBF) associated with increased neuronal activity (neurovascular coupling). In the present work, we investigated the role of NO and of its newly recognized precursor, nitrite, in neurovascular coupling using a well-established rat model of somatosensory stimulation. Biological synthesis of NO of neuronal origin was inhibited pharmacologically. Following the initial uncoupling of neuronal and hemodynamic responses to somatosensory stimulation, the NO donor sodium nitroprusside, added within the range of physiological concentrations, significantly increased, but did not fully restore the functional CBF response. In contrast, nitrite at its physiological concentration fully recovered neurovascular coupling to its original magnitude. The magnitude of the effect is, however, dose-dependent. Sub-physiological concentrations of nitrite were not enough to entirely restore neurovascular coupling and supra-physiological concentrations acted more as a local vasodilator that changed resting CBF and interfered with the functional CBF response. These results suggest that nitrite can be efficiently converted into NO and utilized to support normal cerebrovascular physiology.

Impact of passive vibration on pressure pulse wave characteristics

The augmentation index (AIx), a marker of wave reflection, decreases following acute leg exercise. Passive vibration (PV) causes local vasodilation that may reduce AIx. This study investigated the effects of acute PV on wave reflection and aortic hemodynamics. In a crossover fashion 20 (M=9, F=11) healthy young (22±3 year) participants were randomized to 10 min PV or no vibration control (CON) trials. Subjects rested in the supine position with their legs over a vibration platform for the entire session. Radial waveforms were obtained by applanation tonometry before and after 3 min (Post-3) and 30 min (Post-30) of PV (∼5.37 G) or CON. No change in parameters was found at Post-3. We found significant time-by-trial interactions (P<0.01) at Post-30 for augmented pressure, AIx and second systolic peak pressure (P2), such that these parameters significantly (P<0.05) decreased (-2.3±3.0 mm Hg, -7.2±6.9% and -1.5±3.5 mm Hg, respectively) after PV but not after CON. These findings suggest that acute PV applied to the legs decreases AIx owing to a decrease in wave reflection magnitude (P2). Further research is warranted to evaluate the potential clinical application of PV in populations at an increased cardiovascular risk who are unable to perform conventional exercise.

Abdominal Obesity Impairs Vasodilation and Insulin Sensitivity in Young Women

Insulin-stimulated increases in vasodilation may enhance glucose uptake, however, whether these hemodynamic actions occur under normal physiological conditions and how they are affected by obesity remains unclear. PURPOSE: To determine if ingestion of glucose (75 g) can stimulate sufficient insulin release to increase superficial femoral artery (SFA) vasodilation and leg vascular conductance (VCd) and if this response is affected by fat distribution in obesity (android vs gynoid). METHODS: Subjects (lean: 21±1.0 %fat, 0.82±0.02 WHR, n=8; gynoid: 35±2.4 %fat, 0.79±0.03 WHR, n=4, android: 40±7.2 %fat, 0.95±0.03 WHR, n=4; mean+SD; determined via densitometry and waist-to-hip ratio [WHR]) were studied after a 12 h overnight fast. Heart rate, cardiac output (Q), SFA vessel diameter, VCd, capillary blood glucose (CBG) and plasma insulin (PI) were measured at baseline (after 15 min in the supine position) and at 30 min intervals for 2 h following glucose ingestion. RESULTS: Q was significantly greater in the android group compared to the lean at baseline (android =6.3±1.23 vs lean=4.0±0.88 L·min-1; P=0.043), however, there were no differences within or between groups at any other time point. SFA vasodilation peaked 90 min post-glucose ingestion in both gynoid and lean and was significantly greater than the android group (gynoid =0.33±0.16; lean=0.45±0.33 vs android = -0.30±0.51 mm change from baseline; P<0.04). VCd was similar between groups at baseline (lean=0.69±0.02, gynoid =0.70±0.17, android =0.70±0.24 ml·min-1·mmHg-1; P=0.976), however, at 90 min the lean group nearly doubled their VCd while the gynoid and android groups remained unchanged (lean=1.28±0.12, gynoid =0.78±0.04, android =0.71±0.14 ml·min-1·mmHg-1; P=0.018). Glucose area under the curve (AUC) was significantly greater in the android compared to the lean group (android =15.4±2.1, lean=12.4±1.03 mmol·L-1·2 h-1; P=0.031). Similarly, insulin AUC was significantly increased in the android compared to both the gynoid and lean groups (android =196±88.4 uIU·L-1·2 h-1 vs gynoid =65±32.9 uIU·L-1·2 h-1 vs lean=60±14.8 uIU·L-1·2 h-1; P=0.021). CONCLUSION: Following glucose ingestion, abdominal (android) obesity impairs local SFA vasodilation perhaps due to insulin resistance.

Current views on mechanisms of vasodilation in response to ischemia and hypoxia

Myocardial function (and thus life) is entirely dependent on sufficient O2 supply. Therefore, this supply is extremely well regulated via a refined system of interacting mechanisms. These have been subject to extensive research for more than 100 years. Surprisingly, remarkable dispute still arises among scientists concerning the factors and mechanisms involved in this regulatory system. During ischemia, myocardial cells have been shown to release vasoactive metabolites (eg, H+ and K+ ions, lactic acid, adenosine, and others), which cause spontaneous coronary dilation. On the other hand claims have been made that the endothelium itself could play a key role in hypoxic/ischemic vasodilation by releasing endothelium-derived relaxant factor (EDRF) (NO = nitric oxide) and other still partially unspecified vasoactive substances (eg, prostaglandins). Furthermore, it has been discussed that intravascular O2 tension (pO2) itself would exert a direct effect upon endothelial and/or vascular smooth muscle cells and thus produce per se a local reflectory vasodilation. In contrast, the intravascular CO2 tension has also been shown to act upon coronary vascular resistance during myocardial ischemia. Recently, hints have been made about the membrane potential of arterial smooth muscle cells as a key factor in hypoxia/ischemia vasodilation. However, during hypoxia and metabolic inhibition, the membrane potential seems to be modulated primarily by the action of adenosinetriphosphate-dependent (ATP) potassium channels (K ATP + channels). In conclusion, a number of factors contribute to ischemia/hypoxia-induced vasodilation. The present review contrasts recent findings on ATP-dependent K+ channels with other experimental evidence concerning other mechanisms involved in hypoxic/ischemic vasodilation.

Combined inhibition of nitric oxide and vasodilating prostaglandins abolishes forearm vasodilatation to systemic hypoxia in healthy humans

We tested the hypothesis that nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute independently to hypoxic vasodilatation, and that combined inhibition would reveal a synergistic role for these two pathways in the regulation of peripheral vascular tone. In 20 healthy adults, we measured forearm blood flow (Doppler ultrasound) and calculated forearm vascular conductance (FVC) responses to steady-state (SS) isocapnic hypoxia (O₂ saturation ~85%). All trials were performed during local α- and β-adrenoceptor blockade (via a brachial artery catheter) to eliminate sympathoadrenal influences on vascular tone and thus isolate local vasodilatory mechanisms. The individual and combined effects of NO synthase (NOS) and cyclooxygenase (COX) inhibition were determined by quantifying the vasodilatation from rest to SS hypoxia, as well as by quantifying how each inhibitor reduced vascular tone during hypoxia. Three hypoxia trials were performed in each subject. In group 1 (n = 10), trial 1, 5 min of SS hypoxia increased FVC from baseline (21 ± 3%; P < 0.05). Infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) for 5 min to inhibit NOS during continuous SS hypoxia reduced FVC by -33 ± 3% (P < 0.05). In Trial 2 with continuous NOS inhibition, the increase in FVC from baseline to SS hypoxia was similar to control conditions (20 ± 3%), and infusion of ketorolac for 5 min to inhibit COX during continuous SS hypoxia reduced FVC by -15 ± 3% (P < 0.05). In Trial 3 with combined NOS and COX inhibition, the increase in FVC from baseline to SS hypoxia was abolished (~3%; NS vs. zero). In group 2 (n = 10), the order of NOS and COX inhibition was reversed. In trial 1, five minutes of SS hypoxia increased FVC from baseline (by 24 ± 5%; P < 0.05), and infusion of ketorolac during SS hypoxia had minimal impact on FVC (-4 ± 3%; NS). In Trial 2 with continuous COX inhibition, the increase in FVC from baseline to SS hypoxia was similar to control conditions (27 ± 4%), and infusion of L-NAME during continuous SS hypoxia reduced FVC by -36 ± 7% (P < 0.05). In Trial 3 with combined NOS and COX inhibition, the increase in FVC from baseline to SS hypoxia was abolished (~3%; NS vs. zero). Our collective findings indicate that (1) neither NO nor PGs are obligatory to observe the normal local vasodilatory response from rest to SS hypoxia; (2) NO regulates vascular tone during hypoxia independent of the COX pathway, whereas PGs only regulate vascular tone during hypoxia when NOS is inhibited; and (3) combined inhibition of NO and PGs abolishes local hypoxic vasodilatation (from rest to SS hypoxia) in the forearm circulation of healthy humans during systemic hypoxia.