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 19 recordsLinked to original sources
PubMed1980

Influence of vasodilator therapy on prognosis of acute myocardial infarction in the aged patients. A comparative study between vasodilator-treated group and group treated without vasodilator.

Influence of vasodilator therapy on prognosis of acute myocardial infarction complicated by left heart failure (in Killip classes II and III) was studied in 22 aged patients (mean age; 75.7 years). The patients were retrospectively divided into 2 groups: Group I; 12 patients were treated with isosorbide dinitrate and/or chlorpromazine and Group II; 10 patients were treated with other conventional medical measures. Initial hemodynamic changes on admission were not significantly different between 2 groups. With these treatments mortality rate within 2 weeks of treatment was lower in Group I than in Group II (p less than 0.01), however, cumulative cardiac mortality rate within 18 months did not differ significantly. The present study demonstrated beneficial influence of vasodilator therapy on early prognosis in aged patients, but failed to show prolonged influence on later mortality.

Age Factors↗
PubMed1999

Role of endothelium-derived vasodilators and K(+) channels in ischemic vasodilation of guinea-pig choroidal arterioles.

PURPOSE: To assess the roles of endothelium-derived vasodilators and K(+) channels on metabolic ischemia-induced vasodilation from diameter changes in choroidal arterioles of the guinea-pig. METHODS: The choroid was isolated from the guinea-pig eye-ball, pinned flat on a silicone rubber plate, and superfused with oxygenated warmed (35 degrees C) Krebs solution. Diameters of choroidal arterioles were measured using video microscopy and a computer program for analysis. Vasodilatory effects were examined after the choroid was exposed to glucose-free/NaCN solutions for 10 minutes. The effects of Nomega-nitro-L-arginine (nitroarginine), indomethacin, and K(+)<?Pub Caret> channel inhibitors (glibenclamide [Glib] and charybdotoxin [ChTX]) on ischemic vasodilation were assessed. RESULTS: Reversible vasodilation was observed when the choroid was exposed to glucose-free/NaCN (10(-3) M) solutions. Nitroarginine (10( -4) M), Glib (2x10(-5) M) and ChTX (10(-7) M) significantly inhibited glucose-free/NaCN (10(-3) M)-induced vasodilation by 47%, 62%, and 24%, respectively. No significant inhibitory effect was observed with indomethacin (10(-5) M). Simultaneous application of Glib and ChTX reduced vasodilation by 77%. When Glib and ChTX were added together to nitroarginine, dilation was reduced by 86%. With high K(+) ([K]o = 47.2 mM) Krebs solution, ischemia caused a slight vasodilation (11%), which was significantly inhibited by nitroarginine. CONCLUSIONS: In guinea-pig choroidal arterioles, glucose-free/ NaCN-induced ischemic vasodilation was mainly mediated by NO and K(ATP) channels. A part of NO-mediated vasodilation was induced independent of the opening of K(+) channels.

Animals↗
PubMed2004

Clinical value of vasodilator test with inhaled nitric oxide for predicting long-term response to oral vasodilators in pulmonary hypertension.

Acute vasodilator tests with prostacyclin (PGI2) or inhaled nitric oxide (iNO) are used to select patients with pulmonary arterial hypertension (PAH) who should be treated with oral vasodilators. The haemodynamic effects of PGI2 and iNO are different, and the limits for considering a vasodilator response as significant are controversial. The study was aimed to investigate the diagnostic performance of acute vasodilator testing with iNO and PGI2 in predicting the clinical outcome after 1 year treatment with oral vasodilators. Twenty-seven patients with severe PAH were studied. Nineteen patients were treated with oral vasodilators and their outcome after 1 year was qualified as favourable or unfavourable. The diagnostic performance of vasodilator tests in predicting this outcome was evaluated using receiver operating characteristics (ROC) curves. The acute effects of iNO and PGI2 on pulmonary artery pressure (PAP) were similar. By contrast, PGI2 produced more marked changes on cardiac output and pulmonary vascular resistance than iNO (P<0.05). The evolution at 1 year was favourable in 11 patients and unfavourable in 8. Patients with favourable evolution showed greater decrease of PAP with iNO than with PGI2 (P<0.05). The decrease of PAP with iNO had the greatest predictive value on the clinical outcome (area under ROC curve, 0.83). We conclude that in patients with PAH, acute vasodilator testing with iNO is preferable to PGI2 because it reflects more consistently the changes in pulmonary vascular tone. The acute decrease of PAP with iNO is the best predictor of the long-term response to oral vasodilator treatment.

Administration, Inhalation↗
PubMed2001

Contribution of nerve-axon reflex-related vasodilation to the total skin vasodilation in diabetic patients with and without neuropathy.

OBJECTIVE: To examine the contribution of nerve-axon reflex-related vasodilation to total acetylcholine-induced vasodilation in the skin of normal and diabetic subjects. RESEARCH DESIGN AND METHODS: The skin microcirculation was evaluated at the forearm level in 69 healthy subjects and 42 nonneuropathic diabetic patients and at the foot level in 27 healthy subjects and 101 diabetic patients (33 with neuropathy, 23 with Charcot arthropathy, 32 with peripheral vascular disease and neuropathy, and 13 without complications). Two single-point laser probes were used to measure total and neurovascular vasodilation response to the iontophoresis of 1% acetylcholine, 1% sodium nitroprusside, and deionized water. RESULTS: The neurovascular response to acetylcholine was significantly higher than the response to sodium nitroprusside and deionized water (P < 0.01). At the forearm level, the contribution of neurovascular response to the total response to acetylcholine was 35% in diabetic patients and 31% in control subjects. At the foot level, the contribution was 29% in diabetic patients without neuropathy and 36% in control subjects, while it was significantly diminished in the three neuropathic groups. A significantly lower nonspecific nerve-axon-related vasodilation was observed during the iontophoresis of sodium nitroprusside, which does not specifically stimulate the C nociceptive fibers. CONCLUSIONS: Neurovascular vasodilation accounts for approximately one-third of the total acetylcholine-induced vasodilation at both the forearm and foot levels. The presence of diabetic neuropathy results in reduction of both the total vasodilatory response to acetylcholine and the percentage contribution of neurovascular vasodilation to the total response. Acetylcholine and sodium nitroprusside cause vasodilation in the skin microcirculation through different pathways.

Acetylcholine↗
PubMed1995

Pulmonary vasodilator responses to nicardipine: comparison with other vasodilators.

OBJECTIVES: To determine the direct effect of nicardipine on the pulmonary vascular bed of the intact-chest, spontaneously breathing cat, and to compare its effectiveness as a pulmonary vasodilator with the effectiveness of isoproterenol, nitroglycerin, and sodium nitroprusside. DESIGN: Prospective, controlled animal study. Each animal received all drugs in random order. SETTING: Animal laboratory at a university. SUBJECTS: Experiments were performed in vivo in ten intact-chest, spontaneously breathing cats with controlled pulmonary blood flow and constant left atrial pressure, during conditions of increased pulmonary vascular tone. INTERVENTIONS: Five animals received intralobar injections of nicardipine (0.1 to 100 micrograms), nitroglycerin (0.1 to 10 micrograms), sodium nitroprusside (0.1 to 100 micrograms), and isoproterenol (0.01 to 1 microgram). Injections were made only when lobar arterial pressure had returned to baseline value. In another five animals, nicardipine, nitroglycerin, and sodium nitroprusside were administered intravenously as a continuous drug infusion in incremental doses titrated to produce a 20% reduction in mean systemic arterial pressure. Each dose was infused until lobar and systemic arterial pressures stabilized. A minimum, 30-min interval was allowed between the infusions of these drugs. MEASUREMENTS AND MAIN RESULTS: When pulmonary vascular tone was increased with a thromboxane A2 mimetic (analog), U46619 (a stable prostaglandin endoperoxide analog), intralobar injections of nicardipine caused dose-related decreases in lobar arterial pressure without affecting left atrial pressure. When compared with the other vasodilator agents, the order of potency was isoproterenol >> nitroglycerin > nicardipine = sodium nitroprusside. Isoproterenol reduced mean systemic arterial pressure 10 to 100 times greater than nitroglycerin, nicardipine, or sodium nitroprusside. However, there were no significant differences between the latter three drugs in producing a decrease in mean systemic arterial pressure. When infused intravenously, nitroglycerin caused the largest amount of pulmonary vasodilation for a given amount of systemic vasodilation. There were no significant differences between the pulmonary vasodilator responses of nicardipine and sodium nitroprusside. CONCLUSIONS: In this feline model of increased pulmonary vascular resistance, nicardipine exerts a direct vasodilator effect in vivo on the pulmonary vascular bed. Nicardipine, nitroglycerin, and sodium nitroprusside caused similar decreases in systemic arterial pressure. However, the pulmonary vasodilator effect was greater with nitroglycerin, which suggests that nitroglycerin is more vasoselective for the pulmonary vascular bed than nicardipine or sodium nitroprusside.

Animals↗
PubMed1995

Effects of phorbol ester on vasodilation induced by endothelium-dependent or endothelium-independent vasodilators in the mesenteric arterial bed.

The effects of phorbol ester, phorbol 12-myristate 13-acetate (PMA), on vasodilation induced by endothelium-dependent or independent vasodilators in the mesenteric arterial bed were examined. In mesentery precontracted with methoxamine, acetylcholine (ACh) produced a concentration-dependent vasodilation, but ACh-induced vasodilation was significantly reduced when the tonus of the mesentery was raised by an equieffective concentration of PMA. Sodium nitroprusside (SNP) and forskolin also caused a concentration-dependent relaxation in the mesenteric arterial bed pre-contracted with methoxamine, but could not induce relaxation in mesentery precontracted with PMA. In mesentery precontracted with PMA or methoxamine, ACh-induced vasodilation was significantly inhibited by tetraethylammonium (TEA), but not by ouabain, glibenclamide, or apamin. ACh-induced vasodilation was significantly inhibited by NG-nitro-L-arginine (L-NNA), whereas L-NNA was not capable of effectively inhibiting the ACh-induced vasodilation of the mesentery precontracted with PMA. These results suggest that stimulation of protein kinase C (PKC) by phorbol ester (PMA) in the mesenteric arterial bed inhibits the relaxation of vascular smooth muscle (VSM) in response to cyclic nucleotides. Furthermore, the endothelium of the mesenteric arterial bed may release endothelium-derived hyperpolarizing factor (EDHF), in addition to nitric oxide (NO), into the mesentery.

Acetylcholine↗
PubMed1999

Relative contribution of vasodilator prostanoids and NO to metabolic vasodilation in the human forearm.

Although many factors are thought to contribute to the regulation of metabolic vasodilation in skeletal muscle vasculature, recent interest has focused on the role of the endothelium. We examined the relative roles of nitric oxide (NO) and of vasodilator prostanoids in the control of metabolically induced functional hyperemia in the forearm of humans. In 43 healthy volunteers [24 +/- 5 (SD) yr] we assessed resting and functional hyperemic blood flow (FHBF) in response to 2 min of isotonic forearm exercise before and after inhibition of NO and/or vasodilator prostanoid production with intra-arterial NG-monomethyl-L-arginine (L-NMMA, 2 mg/min) and aspirin (ASA, 3 mg/min), respectively. Blood flow was measured using venous occlusion plethysmography. L-NMMA and ASA decreased resting forearm blood flow by 42% (P < 0.0001) and 23% (P < 0.0001), respectively, whereas infusion of ASA followed by L-NMMA reduced flow by a further 24% (P < 0.05). L-NMMA reduced peak FHBF by 18% [from 13.9 +/- 1.0 to 11.4 +/- 1.1 (SE) ml. 100 ml forearm-1. min-1, P = 0.003] and the volume "repaid" after 1 and 5 min by 25% (8.9 +/- 0.7 vs. 6.7 +/- 0.7 ml/100 ml, P < 0.0001) and 37% (26.6 +/- 1.8 vs. 16.8 +/- 1.6 ml/100 ml, P < 0.0001). ASA similarly reduced peak FHBF by 19% (from 14.5 +/- 1.1 to 11.8 +/- 0.9. 100 ml forearm-1. min-1, P < 0.001) and the volume repaid after 1 and 5 min by 14% (7.5 +/- 0. 6 vs. 6.4 +/- 0.6 ml/100 ml, P = 0.0001) and 20% (21.2 +/- 1.5 vs. 16.9 +/- 1.5 ml/100 ml, P < 0.0001), respectively. The coinfusion of ASA and L-NMMA did not decrease FHBF to a greater extent than either agent alone. These data suggest that endothelium-derived NO and vasodilator prostanoids contribute to resting blood flow and metabolic vasodilation in skeletal muscle vasculature in healthy humans. Although these vasodilator mechanisms operate in parallel in exercise-induced hyperemia, they appear not to be additive. Other mechanisms must also be operative in metabolic vasodilation.

Adult↗
PubMedDate not supplied

Can a single vasodilator be responsible for both coronary autoregulation and metabolic vasodilation?

To test the hypothesis that both coronary autoregulation and metabolic vasodilation can be mediated by the same substance, we have analysed measured autoregulation curves with the aid of a simple mass balance model. In an open-chest dog preparation, increasing the heart rate by pacing results in a nearly parallel shift of the autoregulation curve to a higher flow (Q) level. We assume a unique relationship between vascular conductance and interstitial concentration of a vasodilating substance [A]. Applying a compartmental mass balance, it is possible to predict with a minimum of assumptions the increase of flow between two points with increased production but having the same vasodilator concentration. The simple result of this analysis is: delta Q = delta production/[A]. If the vasodilator concentration varies by more than a factor 2 between low and high conductance points, the autoregulation curve cannot shift in a parallel fashion as a result of an increased production rate, but rather will become less and less steep. We conclude that a single vasodilator cannot be responsible for both autoregulation and metabolic vasodilation unless complex assumptions are made, for which there is as yet no experimental support.

Adenosine↗
PubMed1983

Effect of coronary vasodilation on ventricular fibrillation threshold: role of exogenous vasodilators and perfusion conditions.

Even without myocardial ischemia, coronary blood flow (CBF) constitutes a major determinant of ventricular fibrillation threshold (VFT). To clarify whether abnormal distribution of normal or increased CBF plays any additional role, 14 open-chest chloralose-anesthetized dogs with fixed-normalized heart rate, cardiac output, and systemic arterial pressure and separate servocontrolled left main coronary artery perfusion were studied as follows: VFT was determined first with coronary perfusion pressure (CPP) set at systemic level (80 mm Hg). Then CBF index was fixed at control levels (134.0 +/- 9.5 ml/min X 100 gm-1 LV) and coronary vasodilation was induced by intracoronary infusion of adenosine until CPP decreased to 49.0 +/- 2.0 mm Hg. Myocardial O2 consumption, LV pressure, LV dp/dt, and surface ECG remained unchanged. However, VFT decreased in all trials by about 45% (p less than 0.001). When CPP was reset to 80 mm Hg while maintaining vasodilation, CBF index increased by 90% to 255.4 +/- 15.4 ml/min X 100 gm-1 LV and VFT by 26% (p less than 0.005) from control. Yet these VFT increases in response to intraluminal pharmacologic vasodilation were about 19% (p less than 0.002) lower than expected for similar CBF index increases occurring physiologically. We conclude that intraluminal coronary vasodilation not matched by appropriate CBF increase results in substantial decrease of VFT. Moreover, at comparable increase of CBF, spontaneous physiologic vasodilation is more effective than intraluminal pharmacologic coronary vasodilation in increasing VFT.

Adenosine↗
PubMed1999

Metabolic vasodilation in the human forearm is preserved in hypercholesterolemia despite impairment of endothelium-dependent and independent vasodilation.

OBJECTIVE: Hypercholesterolemia has been shown to impair endothelium-mediated, nitric oxide (NO)-dependent responses to acetylcholine (ACh), serotonin, substance P and flow-mediated dilation. We have recently shown that NO contributes to metabolic vasodilation in the human forearm. We sought to determine whether metabolic vasodilation is impaired in healthy subjects with hypercholesterolemia. METHODS: We compared the forearm blood flow (FBF) responses to isotonic exercise, ACh and the endothelium-independent vasodilator sodium nitroprusside in young, otherwise healthy volunteers with hypercholesterolemia and controls before and after the NO inhibitor NG-monomethyl-L-arginine (L-NMMA). FBF was measured using venous occlusion plethysmography. Hypercholesterolemic (n = 20) and control (n = 20) subjects were age- and gender-matched. RESULTS: Total cholesterol (6.9 +/- 0.3 vs. 4.6 +/- 0.1 mmol/l, P < 0.0001), low density lipoprotein (4.9 +/- 0.4 vs. 2.7 +/- 0.1 mmol/l, P < 0.001) and triglyceride (1.3 +/- 0.2 vs. 0.8 +/- 0.1 mmol/l, P = 0.005) levels were higher in the hypercholesterolemic group. Basal FBF and resistance were similar in the two groups. Hypercholesterolemia impaired the peak FBF response to ACh (11.1 +/- 1.9 vs. 17.6 +/- 2.2 ml/100 ml/min, P = 0.03), and reduced the peak response to sodium nitroprusside (6.0 +/- 0.4 vs. 8.1 +/- 0.6 ml/100 ml/min, P < 0.01). However, hypercholesterolemia did not affect peak hyperemic FBF (13.1 +/- 1.0 vs. 13.2 +/- 1.0 ml/100 ml/min, P = 1.0) or the FBF volume repayment during the 1 or 5 min after exercise. Resting FBF was reduced by L-NMMA to a similar degree (by 33% vs. 40%, P = 0.17) in both groups. Although L-NMMA reduced peak hyperemic FBF (by 16% vs. 17%, P = 0.93) and the volume repaid after exercise in both groups, there were no differences between the two groups. CONCLUSIONS: Exercise-induced metabolic vasodilation is in part dependent on NO release. Hypercholesterolemia impairs NO-mediated vasodilation, but is not associated with a reduction in exercise-induced hyperemia. This may indicate that multiple compensatory mechanisms are operative in skeletal muscle metabolic vasodilation.

Acetylcholine↗
PubMed1989

S-nitrosothiols as vasodilators: implications regarding tolerance to nitric oxide-containing vasodilators.

1. The formation of an S-nitrosothiol compound, S-nitroso-N-acetylcysteine (SNAC) has recently been proposed to mediate the augmentation of the anti-aggregatory and haemodynamic effects of glyceryl trinitrate observed in the presence of N-acetylcysteine. This study investigated the effects on an isolated coronary artery preparation of acute and prolonged exposure to S-nitrosothiol compounds and nitric oxide (NO). 2. Single doses of NO and of the S-nitrosothiol compounds, SNAC and S-nitroso-N-acetyl-penicillamine (SNAP), induced rapid, but transient, relaxations in U46619-contracted bovine isolated coronary artery rings. Peak relaxation responses to SNAP and NO were attenuated in the presence of N-acetylcysteine, cysteine, ascorbic acid and methylene blue. The duration of the relaxation responses to SNAC was two to three times longer than those to SNAP and NO. In the presence of N-acetylcysteine (but not cysteine, ascorbic acid or methylene blue) the duration of the relaxation responses to SNAP and NO (but not to SNAC) was markedly increased. H.p.l.c. assay confirmed that, in the presence of N-acetylcysteine, SNAP and, to a lesser degree, NO were converted to the relatively more stable and longer acting vasodilator, SNAC. 3. When compared to control rings, coronary artery rings superfused with glyceryl trinitrate were subsequently markedly less responsive to the vasodilator actions of glyceryl trinitrate, whereas responsiveness to SNAC or NO was only marginally reduced. On the other hand, coronary artery rings superfused with SNAC or NO were subsequently less responsive to glyceryl trinitrate, SNAC and NO. Thus prolonged vascular exposure to SNAC or NO induced a form of tolerance different from that induced with glyceryl trinitrate and which is possibly associated with impaired guanylate cyclase activity. 4. Coronary artery rings superfused with NO were markedly less responsive to glyceryl trinitrate and NO, whereas responses to the endothelium-dependent vasodilator A23187 and to theophylline were not significantly attenuated. 5. It is concluded that formation of the more stable vasodilator SNAC occurs on incubation of N-acetylcysteine with SNAP or NO. While coronary artery responsiveness to SNAC and NO is virtually unchanged in the presence of glyceryl trinitrate-induced tolerance, after prolonged exposure to SNAC or NO tolerance may develop to these vasodilators with cross-tolerance to glyceryl trinitrate but not A23187. Thus, formation or therapeutic utilization of SNAC may acutely circumvent the problem of glyceryl trinitrate-induced tolerance but, during prolonged vascular exposure to SNAC, attenuation of vascular responsiveness may occur to a wide range of vasodilators.

Acetylcysteine↗
PubMedDate not supplied

The influence of dihydroergotamine on adenosine-induced and reactive coronary vasodilation. Interaction of dihydroergotamine and coronary vasodilation.

The influence of dihydroergotamine on adenosine-induced and reactive vasodilation after long and short periods of coronary artery occlusion was investigated in thoracotomized dogs. Adenosine-induced vasodilation (intracoronary administration) and vasodilation after long periods of coronary artery occlusion (25-35 beats) were similarly influenced, i.e. decreased by the i.v. administration of 10 mug/kg dihydroergotamine. By contrast vasodilation after short periods of coronary artery occlusion (4-7 beats) tended to be increased. This difference in response is thought to arise from two distinct mechanisms of coronary vasodilation after coronary artery occlusion depending on the duration of the occlusion period. The vasodilation after short periods of coronary artery occlusion possibly corresponds to physiological autoregulation. With longer periods of coronary artery occlusion an additional, consecutive mechanism is called into action.

Adenosine↗
PubMed1999

Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilation, and flow-mediated dilation in human coronary circulation.

BACKGROUND: Endothelial dysfunction is associated with atherosclerosis and may contribute to ischemic syndromes. We assessed the contribution of endothelium-derived nitric oxide (NO) and vasodilator prostanoids to resting blood flow, metabolic vasodilation, and flow reserve in the human coronary circulation. METHODS AND RESULTS: Coronary hemodynamics were assessed before and after inhibition of vasodilator prostanoids and NO with intracoronary aspirin (acetylsalicylic acid [ASA]) and N(G)-monomethyl-L-arginine (L-NMMA), respectively. Angiographically smooth or mildly irregular vessels, with normal adenosine-induced coronary flow reserve, were studied in 25 patients undergoing clinically indicated procedures. Coronary blood velocity was measured by Doppler flow wire, and coronary blood flow (CBF) was calculated. ASA reduced resting conduit vessel diameter by 11% (P = 0.003) and CBF by 27% (P = 0.008) and increased coronary vascular resistance (CVR) by 24% (P<0.0001). ASA attenuated pacing-induced hyperemia by 28% (45.0+/-4.6 versus 32.6+/-3.4 mL/min, P = 0.005) and increased minimum CVR by 39% (2.8+/-0.3 versus 3.9+/-0.5 mm Hg x mL(-1) x min(-1), P = 0.007). L-NMMA reduced resting conduit vessel diameter by 9% (P = 0.05) and CBF by 20% (P = 0.08) and increased CVR by 19% (P = 0.03). L-NMMA attenuated pacing-induced hyperemia by 20% (42.4+/-5.1 versus 34.1+/-3.4 mL/min, P = 0.04) and increased minimum CVR by 33% (2.9+/-0.4 versus 3.8+/-0.5 mm Hg x mL(-1) x min(-1), P = 0.02). ASA (7.7+/-2.3% versus -1.6+/-3.2%, P = 0.06) and L-NMMA (12.1+/-3.9% versus 0.0+/-2.9%, P = 0.02) abolished pacing-induced conduit vessel flow-mediated dilation. Conclusions-Tonic release of vasodilator prostanoids and NO contributes to resting conduit and resistance vessel tone and to peak functional hyperemia and flow-mediated dilation after metabolic stimulation. This underscores the importance of normal endothelial function for metabolic vasodilation and suggests that it may be a key mechanism for preventing myocardial ischemia in coronary artery disease.

Adenosine↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed1985

The effectiveness of local injections of vasodilating agents to produce vasodilation in subcutaneous tissue in rabbits.

The isotope washout method has been widely used to study characteristics of the microcirculation in localized vascular beds. Some of these studies have used local injections of vasodilating agents to maximally dilate the vascular bed. This study was undertaken to determine the agent most effective in producing this critical vasodilation. A rabbit model was constructed that allowed the study of the subcutaneous blood flow by either 133Xe and 131I-antipyrine washout. Dose-response curves were constructed for five agents. The agents used and the doses that produced the maximum washout rate, were histamine (100 micrograms), verapamil (0.5 mg), prostaglandin E1 (6 micrograms), papaverine (5 mg) and nitroprusside (60 micrograms). The five agents at these doses were compared with each other, and nitroprusside produced a greater washout rate than papaverine (P less than 0.005), histamine (P less than 0.001) and verapamil (P less than 0.005). There was no difference between nitroprusside and prostaglandin E1 (P greater than 0.01). The effect of three of the agents in producing tissue oedema was examined by comparing the washout rates values obtained with the two isotopes. Both nitroprusside and papaverine produced large oedema whereas histamine resulted in little oedema formation. Nitroprusside, therefore, appears to be the most suitable vasodilating agent for use in studies which require maximum vasodilation of localized vascular beds.

Alprostadil↗
PubMed1988

Pinacidil-induced vascular relaxation: comparison to other vasodilators and to classical mechanisms of vasodilation.

Pinacidil is a potent antihypertensive agent in animals and humans. In conscious spontaneously hypertensive rats after oral administration, pinacidil was approximately 3- and 10-fold more potent than hydralazine and minoxidil, respectively. Likewise, under in vitro conditions, pinacidil (ED50 = 0.3 microM) was more potent in relaxing serotonin-contracted rat aortic strips than either minoxidil (ED50 = 0.1 mM) or hydralazine (ED50 = 0.2 mM). These data are consistent with the contention that pinacidil is a direct-acting vasodilator whereas minoxidil and hydralazine may be converted in vivo to active moieties and/or exert indirect effects more apparent under in vivo than in vitro conditions. The pharmacology of pinacidil appears unrelated to classical mechanism of vasodilation. Pinacidil does not interact with alpha, beta, cholinergic, or histaminergic receptors. Pinacidil does not produce vasodilation via an indirect effect mediated by adenosine, prostaglandin, or endothelial-derived relaxant factor (EDRF) release. Pinacidil does not alter cAMP or cGMP levels and, based on numerous approaches, does not resemble conventional calcium channel antagonists in its vasodilating activity. Thus, a review of the literature presented herein supports the contention that pinacidil-induced vascular relaxation is a direct effect mediated by a novel mechanism.

Animals↗
PubMed2004

Glyburide inhibits dipyridamole-induced forearm vasodilation but not adenosine-induced forearm vasodilation.

BACKGROUND: The mechanism of the vasodilator response to adenosine has not been elucidated in humans. Stimulation of adenosine receptors on endothelial and vascular smooth muscle cells with subsequent endothelial release of nitric oxide and opening of adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels has been suggested. AIM: The aim of this study was to investigate the involvement of K(ATP) channels in the vasodilator response to adenosine and the nucleoside transport inhibitor dipyridamole. Methods and results In healthy male volunteers, adenosine (0.6, 1.9, 5.6, 19, 57, and 190 nmol. min(-1). dL(-1)) was infused into the brachial artery, and forearm blood flow (FBF) was measured by use of strain-gauge plethysmography. Adenosine increased the FBF ratio (FBF in experimental arm/FBF in control arm) from 1.3 +/- 0.2 to 1.2 +/- 0.2, 1.5 +/- 0.2, 2.8 +/- 0.4, 7.3 +/- 2.3, 11.1 +/- 4.1, and 12.9 +/- 3.7 for the six increasing adenosine doses, respectively. Simultaneous infusion of glyburide (INN, glibenclamide), a blocker of K(ATP) channels, did not affect this response (from 1.7 +/- 0.4 to 1.5 +/- 0.2, 2.2 +/- 0.3, 4.0 +/- 1.0, 9.3 +/- 4.0, 13.5 +/- 6.4, and 15.9 +/- 5.3 for the 6 increasing doses of adenosine, respectively; P =.439, n = 6). The increase in FBF ratio during infusion of the nucleoside transport inhibitor dipyridamole (20, 60, and 200 nmol. min(-1). dL(-1)) was significantly reduced by glyburide, as follows: from 1.2 +/- 0.1 to 1.7 +/- 0.2, 2.4 +/- 0.5, and 2.9 +/- 0.4, respectively, during saline solution and from 1.6 +/- 0.2 to 1.8 +/- 0.2, 2.1 +/- 0.3, and 2.2 +/- 0.4, respectively, during glyburide (P =.010 for effect of glyburide on response from baseline, ANOVA for repeated measures; n = 8). The vasodilator response to dipyridamole was significantly inhibited by the adenosine receptor antagonist theophylline. CONCLUSION: Opening of vascular K(ATP) channels is involved in the forearm vasodilator response to dipyridamole but not to adenosine. Differences in stimulated cell type (endothelium for adenosine versus smooth muscle cells for dipyridamole) may underlie this divergent pharmacologic profile.

Adenosine↗
PubMed1998

Neurochemical distinction between skeletal muscle vasodilator neurons and pelvic vasodilator neurons in guinea-pigs.

This study sets out to compare the combinations of potential vasodilator transmitters expressed by sympathetic and pelvic vasodilator neurons of guinea-pigs. Triple-labelling fluorescence immunohistochemistry was used to examine immunoreactivity (IR) to vasoactive intestinal peptide (VIP), nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) in lumbar sympathetic ganglia, and in perivascular axons supplying hindlimb skeletal muscles or pelvic viscera. Only 0.2% of VIP-IR nerve cell bodies in lumbar sympathetic ganglia (n = 4632 VIP-IR nerve cell profiles) contained NOS-IR, and one VIP-IR neuron contained CGRP-IR. The VIP-IR perivascular axons along the common and external iliac arteries, femoral artery and arteries to hindlimb muscles lacked NOS-IR and CGRP-IR. In contrast, all VIP-IR perivascular axons projecting from pelvic ganglia to the main uterine artery, and half of the VIP-IR axons along the internal iliac artery, contained NOS-IR and CGRP-IR. Thus, the neurochemical content of sympathetic vasodilator neurons to skeletal muscle arteries was clearly distinguishable from that of pelvic vasodilator neurons to the uterine vasculature. Furthermore, the autonomic dilation in each vascular bed is likely to be qualitatively different, and matched to the functional requirements of each target organ.

Animals↗