Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “vasodilation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1993

Profile of paediatric patients with pulmonary hypertension judged by responsiveness to vasodilators.

OBJECTIVE: To describe the demographic and haemodynamic variables of children presenting with primary pulmonary hypertension or pulmonary hypertension appearing or persisting after surgical correction of congenital heart defects and to assess the acute effect of vasodilator drugs on their pulmonary vascular bed. DESIGN: Retrospective review. SETTING: Paediatric cardiology department and intensive care unit of a large tertiary centre. PATIENTS: Fourteen consecutive patients presenting with primary pulmonary hypertension (group 1) or pulmonary hypertension persisting or appearing late after complete surgical repair (group 2). INTERVENTION: Baseline haemodynamic measurements were taken in room air at rest and repeated in 100% oxygen. With constant monitoring of heart rate and pulmonary and systemic arterial pressures, patients were given serial intravenous, sublingual, or oral incremental doses of vasodilators (mean 4.1 trials per patient). The maximum effect of the drug was charted. MAIN OUTCOME MEASURES: A positive response to acute vasodilator tests was defined as a decrease in mean pulmonary or mean systemic arterial pressure > 15% with the mean pulmonary artery pressure not reaching the systemic level and either no change or an increase in mean systemic arterial pressure. Haemodynamic variables between groups (1 v 2, responders v non-responders, patients experiencing or not experiencing adverse effects to vasodilators) were compared by a two tailed unpaired Student's t test, and their survival curves were compared by the log rank statistic. RESULTS: Groups are small and definitive conclusions are difficult to draw, but the baseline haemodynamic assessments were not significantly different between group 1 and 2 or between responders and non-responders to vasodilators. Patients experiencing adverse effects had a higher pulmonary vascular resistance (p = 0.04) and wedge pressure (p = 0.02) than those without adverse effects. Of the vasodilators used, tolazoline, hydralazine, salbutamol, phentolamine, and phenoxybenzamine were ineffective. A positive response was seen in five of 13 patients given oxygen, in one of eight given prostacyclin, four of 12 given nifedipine, four of eight given diltiazem, one of six given captopril, and two of seven given glyceryl trinitrate. Estimates of survival of the population with primary pulmonary hypertension were 37% at one year and 12% at 2.5 years. Survival was significantly shorter in the non-responders than in the responders (p = 0.005). CONCLUSION: Children with primary pulmonary hypertension present to the cardiologist at a young age (five of eight were younger than 7 years) but with advanced pulmonary vascular disease and have a poor prognosis. 64% of group 1 and group 2 patients had a positive response to acute treatment with at least one vasodilator. Calcium channel blockers were the most effective agents. There was a positive response to drugs despite a negative response to acute treatment with oxygen. The survival of non-responders was shorter than that of the responders.

Adolescent↗
PubMed2005

Sensory peptide neurotransmitters mediating mucosal and distension evoked neural vasodilator reflexes in guinea pig ileum.

The aim was to determine the role CGRP and/or tachykinins released from sensory neural mechanisms in enteric neural vasodilator pathways. These pathways project through the myenteric plexus to submucosal vasodilator neurons. Submucosal arterioles were exposed in the distal portion of an in vitro combined submucosal-myenteric guinea pig ileal preparation, and dilation was monitored with videomicroscopy. Vasodilator neural reflexes were activated by gently stroking the mucosa with a fine brush or by distending a balloon placed beneath the flat-sheet preparation in the proximal portion. Dilations evoked by mucosal stroking were inhibited 64% by the CGRP 8-37 and 37% by NK3 (SR 142801) antagonists. When the two antagonists were combined with hexamethonium, only a small vasodilation persisted. Balloon distension-evoked vasodilations were inhibited by NK3 antagonists (66%) but were not altered by CGRP 8-37. In preparations in which myenteric descending interneurons were directly activated by electrical stimulation, combined application of CGRP 8-37 and the NK antagonists had no effect. Stimulation of capsaicin sensitive nerves in the myenteric plexus did not activate these vasodilator reflexes. These findings suggest that mucosal-activated reflexes result from the release of CGRP and tachykinins from enteric sensory neurons. Distension-evoked responses were significantly blocked by NK3 antagonists, suggesting that stretch activation of myenteric sensory neurons release tachykinins that activate NK3 receptors on myenteric vasodilator pathways.

Animals↗
PubMed2004

Time course of flow-induced vasodilation in skeletal muscle: contributions of dilator and constrictor mechanisms.

The purpose of this study was to determine the time course of flow-induced vasodilation in soleus and gastrocnemius muscle arterioles and the mechanisms that underlie vasodilatory responses to an increase in intraluminal flow. Vasodilation was assessed during 20 min of continuous exposure to intraluminal flow. Both soleus and gastrocnemius muscle arterioles dilated in response to flow, although the magnitude of vasodilation was greater in arterioles from the gastrocnemius muscle. Neither blockade of nitric oxide synthase with N(G)-nitro-L-arginine methyl ester (L-NAME) nor blockade of cyclooxygenase with indomethacin inhibited the initial vasodilation (0-2 min) in arterioles from either muscle. In contrast, vasodilation to sustained exposure to flow (2-20 min) was eliminated by treatment with L-NAME in arterioles from both muscles. Both depolarization with 40 mM KCl and blockade of Ca(2+)-activated K(+) channels inhibited the initial flow-induced dilation, and the inhibition was greater in gastrocnemius muscle arterioles than soleus muscle arterioles. In the presence of L-NAME, prolonged exposure to flow resulted in constriction in soleus and gastrocnemius muscle arterioles. This constriction was abolished by endothelin receptor blockade. These results indicate that the time course and magnitude of flow-induced vasodilation differs between arterioles from soleus and gastrocnemius muscles. The immediate response to increased flow is greater in gastrocnemius muscle arterioles and involves activation of K(+) channels. In arterioles from both soleus and gastrocnemius muscles, vasodilation to sustained flow exposure occurs primarily through production of nitric oxide. In the absence of nitric oxide, sustained exposure to flow results in pronounced constriction that is mediated by endothelin.

Animals↗
PubMed2003

EDHF-mediated vasodilation involves different mechanisms in normotensive and hypertensive rat lungs.

The role of endothelium-derived hyperpolarizing factor (EDHF) in regulating the pulmonary circulation and the participation of cytochrome P-450 (CYP450) activity and gap junction intercellular communication in EDHF-mediated pulmonary vasodilation are unclear. We tested whether tonic EDHF activity regulated pulmonary vascular tone and examined the mechanism of EDHF-mediated pulmonary vasodilation induced by thapsigargin in salt solution-perfused normotensive and hypoxia-induced hypertensive rat lungs. After blockade of both cyclooxygenase and nitric oxide synthase, inhibition of EDHF with charybdotoxin plus apamin did not affect either normotensive or hypertensive vascular tone or acute hypoxic vasoconstriction but abolished thapsigargin vasodilation in both groups of lungs. The CYP450 inhibitors 7-ethoxyresorufin and sulfaphenazole and the gap junction inhibitor palmitoleic acid, but not 18alpha-glycyrrhetinic acid, inhibited thapsigargin vasodilation in normotensive lungs. None of these agents inhibited the vasodilation in hypertensive lungs. Thus tonic EDHF activity does not regulate either normotensive or hypertensive pulmonary vascular tone or acute hypoxic vasoconstriction. Whereas thapsigargin-induced EDHF-mediated vasodilation in normotensive rat lungs involves CYP450 activity and might act through gap junctions, the mechanism of vasodilation is apparently different in hypertensive lungs.

Animals↗
PubMed2002

Nitric oxide and attenuated reflex cutaneous vasodilation in aged skin.

Thermoregulatory cutaneous vasodilation is diminished in the elderly. The goal of this study was to test the hypothesis that a reduction in nitric oxide (NO)-dependent mechanisms contributes to the attenuated reflex cutaneous vasodilation in older subjects. Seven young (23 +/- 2 yr) and seven older (71 +/- 6 yr) men were instrumented with two microdialysis fibers in the forearm skin. One site served as control (Ringer infusion), and the second site was perfused with 10 mM N(G)-nitro-l-arginine methyl ester to inhibit NO synthase (NOS) throughout the protocol. Water-perfused suits were used to raise core temperature 1.0 degrees C. Red blood cell (RBC) flux was measured with laser-Doppler flowmetry over each microdialysis fiber. Cutaneous vascular conductance (CVC) was calculated as RBC flux per mean arterial pressure, with values expressed as a percentage of maximal vasodilation (infusion of 28 mM sodium nitroprusside). NOS inhibition reduced CVC from 75 +/- 6% maximal CVC (CVC(max)) to 53 +/- 3% CVC(max) in the young subjects and from 64 +/- 5% CVC(max) to 29 +/- 2% CVC(max) in the older subjects with a 1.0 degrees C rise in core temperature. Thus the relative NO-dependent portion of cutaneous active vasodilation (AVD) accounted for approximately 23% of vasodilation in the young subjects and 60% of the vasodilation in the older subjects at this level of hyperthermia (P < 0.001). In summary, NO-mediated pathways contributed more to the total vasodilatory response of the older subjects at high core temperatures. This suggests that attenuated cutaneous vasodilation with age may be due to a reduction in, or decreased vascular responsiveness to, the unknown neurotransmitter(s) mediating AVD.

Adult↗
PubMed1979

Contributions of nerves and metabolites to exercise vasodilation: a unifying hypothesis.

Neuronal cell bodies exist in arterioles of skeletal muscle and appear to initiate vasodilation during phasic contraction. The following findings indicate that intrinsic nerves rather than metabolites maintain vasodilation during sustained phasic contraction with free flow. 1) Under certain conditions maximal vasodilation can occur without detectable release of metabolites. 2) When metabolites are released during exercise, their concentrations in blood or tissue do not always determine the extent of vasodilation. 3) Vasodilation during sustained contraction can be partly blocked by local anesthetics. The extent of block is inversely proportional to the concentration of metabolites. Dose, time course of block, and other tests of specificity indicate that local anesthetics act on the intrinsic nerves rather than smooth or striated muscle. When contraction stops, neurogenic vasodilation decays rapidly (half time less than 1 min). Sustained vasodilation during recovery is therefore fully accounted for by metabolites. A hypothesis is suggested that integrates the roles of extrinsic nerves, intrinsic nerves, and metabolites in support of muscle contraction.

Action Potentials↗
PubMed1992

Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation.

Vasodilation following the infusion of acetylcholine is due to the release of endothelium-derived relaxing factor (EDRF). However, the role of EDRF in neurogenic coronary vasodilation, when acetylcholine is released outside the vessel at the adventitial-medial junction, has not been established. The action of EDRF in parasympathetic coronary vasodilation was tested in the present study using a specific inhibitor of EDRF synthesis, nitro-L-arginine methyl ester (L-NAME). Experiments were conducted on closed-chest, alpha-chloralose-anesthetized dogs with the heart paced at a constant rate. Phentolamine and propranolol were administered to block alpha- and beta-adrenergic receptors, and ibuprofen was given to inhibit prostaglandin synthesis. Intracoronary infusion of L-NAME decreased the coronary vasodilation in response to intracoronary acetylcholine or vagal stimulation. The coronary response to the endothelium-independent vasodilator nitroglycerin was unaffected by L-NAME. These data demonstrate that L-NAME specifically inhibits coronary vasodilation caused by acetylcholine and vagal stimulation, indicating that parasympathetic coronary vasodilation is dependent on EDRF.

Animals↗
PubMed1994

Permissive role of prostacyclin in cerebral vasodilation to hypercapnia in newborn pigs.

Hypercapnic cerebral vasodilation in piglets is accompanied by increased cerebral prostanoid synthesis. Interventions that prevent the increased prostanoids also interfere with the vasodilation. However, the increased prostanoids may not produce vasodilation directly; instead, they may allow or enhance function of another mechanism. The present experiments examined the hypothesis that prostacyclin can allow, but may not directly produce, cerebral vasodilation to hypercapnia. Chloralose-anesthetized piglets were equipped with closed cranial windows for measurements of pial arteriolar diameters. Hypercapnia (arterial CO2 partial pressure approximately 70 mmHg) was administered before and after indomethacin (5 mg/kg iv) in all animals. Then artificial cerebrospinal fluid (aCSF) under the cranial window was replaced for the remainder of the experiment with aCSF containing vehicle, carbaprostacyclin (60 pM), iloprost (1 pM), prostaglandin E2 (PGE2; 1.7 and 3.3 nM), isoproterenol (10 and 100 nM), or sodium nitroprusside (1 microM), and hypercapnia was repeated. The two prostacyclin receptor agonists restored cerebral vasodilation to hypercapnia that had been blocked by indomethacin (to 92 +/- 31% and 76 +/- 11% of the before-indomethacin dilation for carbaprostacyclin and iloprost, respectively.) The highest dose of PGE2 partially restored the dilation (43 +/- 7% of the pre-indomethacin response). In contrast, neither isoproterenol nor sodium nitroprusside permitted significant dilation to hypercapnia following indomethacin treatment. These data indicate that prostacyclin can allow hypercapnic vasodilation to occur, but increasing levels do not appear to be necessary to cause the dilation directly. The short half-life of prostacyclin may explain why active prostanoid synthesis appears to be necessary for hypercapnia-induced cerebral vasodilation in newborn pigs.

Animals↗
PubMed1994

Adenosine A1-receptor mechanisms antagonize beta-adrenergic pulmonary vasodilation in hypoxia.

Hypoxic pulmonary vasoconstriction is refractory to beta-adrenergic receptor (beta-AR)-mediated pulmonary vasodilation. We hypothesized that hypoxic pulmonary arteries release adenosine (Ado) that antagonizes beta-AR-mediated pulmonary vasodilation. Using isolated rat pulmonary artery rings, we investigated 1) the effect of hypoxia and exogenous Ado on beta-AR-mediated pulmonary vasodilation, 2) the intracellular site of dysfunctional beta-AR-mediated pulmonary vasodilation in hypoxia, and 3) the Ado receptor subtype responsible for dysfunction of beta-AR-mediated pulmonary vasodilation. Hypoxia attenuated normal beta-AR-mediated pulmonary vasodilation to isoproterenol (97.5 +/- 0.8 vs. 71.5 +/- 2.3%, P < 0.01). In contrast, forskolin induced the same vasorelaxation in hypoxic pulmonary rings as controls (P = 0.09). Incubation of normoxic rings with Ado attenuated the vasorelaxation response induced by beta-AR stimulation (71.5 +/- 5.9%, P < 0.01), similar to the effect observed in hypoxia. Both nonspecific Ado receptor blockade (8-sulfophenyl-theophylline) and specific A1-receptor blockade (8-cyclopentyl-1,3-dimethylxanthine) restored the vasorelaxation response of hypoxic rings induced by beta-AR stimulation (93.3 +/- 2.3 and 92.2 +/- 2.8%, P < 0.01). The effects of hypoxia and Ado were reproduced by a specific A1 agonist (2-chloro-N6-cyclopentyladenosine), demonstrating impaired vasorelaxation induced by beta-AR stimulation in normoxia (70.6 +/- 4.5%, P < 0.01). From these data, we conclude that hypoxia antagonizes beta-AR-mediated pulmonary vasodilation via an Ado A1-receptor mechanism.

Adenosine↗
PubMed1996

Coronary arteriolar flow-induced vasodilation signals through tyrosine kinase.

Coronary arterioles demonstrate flow-dependent vasodilation that is mediated by endothelial release of nitric oxide. The signaling mechanisms for this response remain unknown. Because tyrosine kinases are an enzyme family linked to many signaling pathways, including some for mechanosensitive transduction, we hypothesized that tyrosine kinase activation is a critical step in flow-induced vasodilation. To test this hypothesis, coronary arterioles were isolated, cannulated with micropipettes, and perfused by two independent reservoir systems. Intraluminal pressure was set at 60 cmH2O, and flow was generated by changing the heights of the reservoirs in equal and opposite directions, thus establishing a pressure difference across the arteriole without altering intraluminal pressure. Vasodilatory responses to intraluminal flow and substance P (1 x 10(-12) to 1 x 10(-7) M) were evaluated before and after intraluminal application of the tyrosine kinase inhibitors genistein (5 microM) and piceatannol (10 microM). Exposure to these inhibitors did not alter spontaneous tone. Substance P caused dose-dependent vasodilation that was not affected by genistein or piceatannol. Increases in intraluminal flow (generated by pressure differences ranging from 4 to 60 cmH2O) elicited graded increases in diameter. Both genistein and piceatannol inhibited the vasodilatory responses to flow. Treatment with daidzein, an inactive analogue of genistein, had no effect on either the flow-induced responses or substance P-induced vasodilation. To further confirm that tyrosine kinase activation is involved in flow-induced vasodilation, vessels were exposed to flow in the absence or presence of genistein and subsequently stained with a fluorescein isothiocyanate-labeled phosphotyrosine antibody. Exposure to flow significantly increased fluorescence of endothelial cells. Genistein treatment reversed the flow-induced increase in tyrosine phosphorylation. These results indicate that endothelium-dependent, flow-induced vasodilation in isolated porcine coronary arterioles is accompanied by an increase in tyrosine kinase activity. We conclude that endothelium-dependent, nitroxidergic, flow-induced vasodilation is mediated, at least in part, by a signaling pathway involving a tyrosine kinase.

Animals↗
PubMed1997

Role of nitric oxide in vasodilator response induced by salbutamol in rat diaphragmatic microcirculation.

To determine the contribution of nitric oxide (NO) to the vasodilator response induced by salbutamol in diaphragmatic microcirculation, we studied a diaphragmatic preparation in anesthetized rats. With bicarbonate-buffered Ringer solution continuously suffusing the diaphragm, laser-Doppler flowmetry was used to record microvascular blood flow (QLDF). The drugs were applied to the surface of the diaphragm. Salbutamol (3.2 x 10(-7)-10(-4) M), isoproterenol (3.2 x 10(-8)-3.2 x 10(-6) M), and forskolin (3.2 x 10(-7)-10(-5) M) each elicited a concentration-dependent increase in QLDF. The vasodilator response induced by salbutamol (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M) was attenuated by a 15-min suffusion of N omega-nitro-L-arginine (L-NNA, 10(-4) M), and pretreatment with L-arginine (10(-2) M) could restore salbutamol-induced vasodilator responses. Salbutamol-induced vasodilation was also abolished by propranolol (10(-5) M). Similarly, the vasodilator response elicited by isoproterenol (3.2 x 10(-8), 10(-7), and 3.2 x 10(-7) M) and forskolin (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M) was inhibited by L-NNA (10(-4) M). In contrast, the vasodilator response induced by adenosine (10(-6), 10(-5), and 10(-4) M) was not affected by L-NNA (10(-4) M). These data indicate that in rat diaphragmatic microcirculation salbutamol-induced vasodilation may be partly mediated by beta-adrenoceptors on the endothelium. Moreover, these data suggest that an elevation of cyclic AMP in the endothelium may cause release of NO.

Adenosine↗
PubMed1998

Role of K+ channels in arteriolar vasodilation mediated by integrin interaction with RGD-containing peptide.

Integrins are transmembrane adhesion receptors found on most cells, including vascular smooth muscle cells. Several integrins bind to the conserved amino acid sequence Arg-Gly-Asp (RGD), and synthetic RGD-containing peptides can cause endothelium-independent arteriolar vasodilation by interacting with the alphavbeta3-integrin expressed by vascular smooth muscle. We hypothesized that RGD peptide-induced vasodilation involves K+ channels. Rat cremaster arterioles were treated with cRGD (GPenGRGDSPCA) in the presence or absence of the nonselective K+ channel inhibitor tetraethylammonium (TEA, 20 mM). TEA caused arterioles to constrict by 19 +/- 5% and inhibited cRGD-induced vasodilation (n = 7, P < 0.05). Vessels preconstricted with phenylephrine (5 x 10(-7) M) showed no significant inhibition of the dilatory response to cRGD, indicating that inhibition by TEA was not related to increased vasomotor tone. Further evidence for the involvement of K+ channels was obtained by addition of 100 mM KCl (n = 5), which inhibited vasodilation caused by cRGD. Inhibition of large and small conductance, Ca2+-activated K+ channels with iberiotoxin (100 nM) or apamin (25 nM), respectively, had no effect on cRGD-induced vasodilation. Partial inhibition of vasodilation was observed with inhibitors of voltage-gated (4-aminopyridine, 1 mM), ATP-sensitive (glibenclamide, 1 microM), and inward rectifying (barium, 50 microM) K+ channels. These data support the hypothesis that integrin-signaling pathways leading to arteriolar vasodilation may involve modulation of K+ channel function.

Animals↗
PubMed2003

Contribution of oxygen radicals to altered NO-dependent pulmonary vasodilation in acute and chronic hypoxia.

Chronic hypoxia (CH) increases pulmonary arterial endothelial nitric oxide (NO) synthase (NOS) expression and augments endothelium-derived nitric oxide (EDNO)-dependent vasodilation, whereas vasodilatory responses to exogenous NO are attenuated in CH rat lungs. We hypothesized that reactive oxygen species (ROS) inhibit NO-dependent pulmonary vasodilation following CH. To test this hypothesis, we examined responses to the EDNO-dependent vasodilator endothelin-1 (ET-1) and the NO donor S-nitroso-N-acetyl penicillamine (SNAP) in isolated lungs from control and CH rats in the presence or absence of ROS scavengers under normoxic or hypoxic ventilation. NOS was inhibited in lungs used for SNAP experiments to eliminate influences of endogenously produced NO. Additionally, dichlorofluorescein (DCF) fluorescence was measured as an index of ROS levels in isolated pressurized small pulmonary arteries from each group. We found that acute hypoxia increased DCF fluorescence and attenuated vasodilatory responses to ET-1 in lungs from control rats. The addition of ROS scavengers augmented ET-1-induced vasodilation in lungs from both groups during hypoxic ventilation. In contrast, upon NOS inhibition, DCF fluorescence was elevated and SNAP-induced vasodilation diminished in arteries from CH rats during normoxia, whereas acute hypoxia decreased DCF fluorescence, which correlated with augmented reactivity to SNAP in both groups. ROS scavengers enhanced SNAP-induced vasodilation in normoxia-ventilated lungs from CH rats similar to effects of hypoxic ventilation. We conclude that inhibition of NOS during normoxia leads to greater ROS generation in lungs from both control and CH rats. Furthermore, NOS inhibition reveals an effect of acute hypoxia to diminish ROS levels and augment NO-mediated pulmonary vasodilation.

Animals↗
PubMed1995

Neutral endopeptidase modulates substance P-induced vasodilation in vivo.

The purpose of this study was to investigate whether neutral endopeptidase (NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral mucosa in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (44-70 microns) in the hamster cheek pouch during suffusion of capsaicin and substance P. We found that capsaicin (0.1 and 10.0 nM) induced significant concentration-dependent vasodilations (13 +/- 4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P < 0.05). Substance P (0.1 and 10.0 nM) also induced significant concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from baseline, respectively; P < 0.05) that were mediated by the COOH-terminal of the molecule. Substance P-induced responses were significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10% increase from baseline, respectively; P < 0.05) and thiorphan (10.0 microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from baseline, respectively; P < 0.05). Substance P-(1-9) had no significant effects on arteriolar diameter. Suffusion of captopril, leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid together had no significant effects on substance P-induced vasodilation. Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These data indicate that NEP modulates substance P-induced vasodilation in the hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP activity may amplify neurogenic vasodilation in the oral mucosa.

Animals↗
PubMed1995

Role of G proteins in the vasodilator response to endothelin isopeptides in vivo.

The purpose of the present study was to determine the influence of pertussis toxin (PTX) on the pulmonary and systemic vasodilator responses to endothelin (ET) isopeptides in the intact cat under conditions of constant pulmonary blood flow and left atrial pressure. When pulmonary vasomotor tone was actively increased by an intralobar arterial infusion of U-46619, intralobar arterial bolus injections of ET-1, ET-2, and ET-3 decreased lobar arterial pressure and systemic vascular resistance in a dose-related manner. The vasodilator responses to ET-1 and ET-2 in the cat lung were abolished by PTX pretreatment, whereas PTX pretreatment did not alter the pulmonary vasodilator response to ET-3 and cromakalim, a specific ATP-sensitive potassium (KATP) channel activator, and the systemic vasodilator responses to all ET isopeptides studied. Glipizide, an inhibitor of KATP channels, inhibited the pulmonary vasodilator responses to ET-1, ET-2, and ET-3, whereas the systemic vasodilator responses to these isopeptides were not changed. The present data are the first to provide a functional correlate in vivo suggesting the existence of different signal transduction mechanisms for two pulmonary vascular ET receptor subtypes, ETA-like that is PTX sensitive and has greater sensitivity to ET-1 and ET-2 (than to ET-3) and ETc-like that is PTX insensitive and has sensitivity to ET-3 (than to ET-1 and ET-2). However, both ET-receptor subtypes promote vasodilation in the adult pulmonary vascular bed by activating KATP channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Nitric oxide and vasodilation in human limbs.

Both the skeletal muscle and skin of humans possess remarkable abilities to vasodilate. Marked vasodilation can be seen in these vascular beds in response to a variety of common physiological stimuli. These stimuli include reactive hyperemia (skin and muscle), exercise hyperemia (muscle), mental stress (muscle), and whole body heating (skin). The physiological mechanisms that cause vasodilation in response to these stimuli are poorly understood, and the substance(s) responsible for it remain unclear. In this context, recent attention has been focused on the possible contribution of nitric oxide (NO) to the regulation of hyperemic responses in human skin and skeletal muscle. The emerging picture is that NO is not an essential component of the dilator response seen during reactive hyperemia. However, it does appear that NO may play a modest role in exercise hyperemia. NO appears to play a major role in the skeletal muscle vasodilation seen in response to mental stress in humans. Preliminary evidence also indicates that NO is not essential for the normal dilator responses observed in the cutaneous circulation during body heating in humans, but this issue needs further study. There are a number of possible mechanisms that might mediate NO release in humans, and the role of these mechanisms in the various hyperemic responses is also poorly understood. The role of altered NO-mediated vasodilation in some disease states is also discussed. Whereas NO is a potent vasodilating substance, the actions of NO alone do not explain a variety of poorly understood vasodilator mechanisms in conscious humans. Much work remains for those interested in the role of NO in the regulation of blood flow to the skin and skeletal muscle of humans.

Animals↗
PubMed2000

Feedforward sympathetic coronary vasodilation in exercising dogs.

The hypothesis that exercise-induced coronary vasodilation is a result of sympathetic activation of coronary smooth muscle beta-adrenoceptors was tested. Ten dogs were chronically instrumented with a flow transducer on the circumflex coronary artery and catheters in the aorta and coronary sinus. During treadmill exercise, coronary venous oxygen tension decreased with increasing myocardial oxygen consumption, indicating an imperfect match between myocardial blood flow and oxygen consumption. This match was improved after alpha-adrenoceptor blockade with phentolamine but was significantly worse than control after alpha + beta-adrenoceptor blockade with phentolamine plus propranolol. The response after alpha-adrenoceptor blockade included local metabolic vasodilation plus a beta-adrenoceptor vasodilator component, whereas the response after alpha + beta-adrenoceptor blockade contained only the local metabolic vasodilator component. The large difference in coronary venous oxygen tensions during exercise between alpha-adrenoceptor blockade and alpha + beta-adrenoceptor blockade indicates that there is significant feedforward beta-adrenoceptor coronary vasodilation in exercising dogs. Coronary venous and estimated myocardial interstitial adenosine concentrations did not increase during exercise before or after alpha + beta-adrenoceptor blockade, indicating that adenosine levels did not increase to compensate for the loss of feedforward beta-adrenoceptor-mediated coronary vasodilation. These results indicate a meaningful role for feedforward beta-receptor-mediated sympathetic coronary vasodilation during exercise.

Adenosine↗
PubMed2003

Cutaneous active vasodilation in humans during passive heating postexercise.

The hypothesis that exercise causes an increase in the postexercise esophageal temperature threshold for onset of cutaneous vasodilation through an alteration of active vasodilator activity was tested in nine subjects. Increases in forearm skin blood flow and arterial blood pressure were measured and used to calculate cutaneous vascular conductance at two superficial forearm sites: one with intact alpha-adrenergic vasoconstrictor activity (untreated) and one infused with bretylium tosylate (bretylium treated). Subjects remained seated resting for 15 min (no-exercise) or performed 15 min of treadmill running at either 55, 70, or 85% of peak oxygen consumption followed by 20 min of seated recovery. A liquid-conditioned suit was used to increase mean skin temperature ( approximately 4.0 degrees C/h), while local forearm temperature was clamped at 34 degrees C, until cutaneous vasodilation. No differences in the postexercise threshold for cutaneous vasodilation between untreated and bretylium-treated sites were observed for either the no-exercise or exercise trials. Exercise resulted in an increase in the postexercise threshold for cutaneous vasodilation of 0.19 +/- 0.01, 0.39 +/- 0.02, and 0.53 +/- 0.02 degrees C above those of the no-exercise resting values for the untreated site (P < 0.05). Similarly, there was an increase of 0.20 +/- 0.01, 0.37 +/- 0.02, and 0.53 +/- 0.02 degrees C for the treated site for the 55, 70, and 85% exercise trials, respectively (P < 0.05). It is concluded that reflex activity associated with the postexercise increase in the onset threshold for cutaneous vasodilation is more likely mediated through an alteration of active vasodilator activity rather than through adrenergic vasoconstrictor activity.

Adrenergic Agents↗