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Clinical and Experimental Pharmacology... 1985The effects of removing the endothelium of the rabbit central ear artery on the response to noradrenaline have been examined in vitro. A 10 mm segment of this artery was...
The effects of removing the endothelium of the rabbit central ear artery on the response to noradrenaline have been examined in vitro. A 10 mm segment of this artery was cannulated and connected to a constant flow perfusion circuit; the endothelium of some arteries was first removed mechanically. Vasomotor activity was determined by measuring the pressure at the input to the artery. Scanning electron microscopy, light microscopy and functional test with acetylcholine on intact and rubbed arteries showed that the endothelium had been effectively removed in lesioned arteries and remained intact in control arteries throughout the experiment. Internal or external noradrenaline-induced a concentration-dependent constriction which was significantly greater in the rubbed arteries. In contrast, there was no significant difference in the pressure/flow curves of control and rubbed arteries whether preconstricted with K+ or not. We conclude that the endothelium in the rabbit isolated ear artery greatly influences the response to internal or external noradrenaline, and that this effect cannot be explained by changes in the physical characteristics of de-endothelialized arteries. The endothelium thus may play an inhibitory role in noradrenaline-induced vasoconstrictions.
Topics: Animals; Arteries; Ear; Endothelium; Microscopy, Electron, Scanning; Muscle, Smooth, Vascular; Norepinephrine; Rabbits; Regional Blood Flow; Vasoconstriction
PubMed: 4006319
DOI: 10.1111/j.1440-1681.1985.tb02320.x -
Biomedicine & Pharmacotherapy =... Feb 2017Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by...
Coronary artery vasospasm (constriction) caused by reduced nitric oxide bioavailability leads to myocardial infarction. Reduced endothelial release of nitric oxide by the neurotransmitter acetylcholine, leads to paradoxical vasoconstriction as it binds to smooth muscle cell M3 receptors. Thus, inhibition of coronary artery vasospasm will improve clinical outcomes. Inhibition of insulin regulated aminopeptidase has been shown to improve vessel function, thus we tested the hypothesis that HFI419, an inhibitor of insulin regulated aminopeptidase, could reduce blood vessel constriction to acetylcholine. The abdominal aorta was excised from New Zealand white rabbits (n=15) and incubated with 3mM Hcy to induce vascular dysfunction in vitro for 1h. HFI419 was added 5min prior to assessment of vascular function by cumulative doses of acetylcholine. In some rings, vasoconstriction to acetylcholine was observed in aortic rings after pre-incubation with 3mM homocysteine. Incubation with HFI419 inhibited the vasoconstrictive response to acetylcholine, thus improving, but not normalizing, vascular function (11.5±8.9% relaxation vs 79.2±37% constriction, p<0.05). Similarly, in another group with mild vasoconstriction, HFI419 inhibited this effect (34.9±4.6% relaxation vs 11.1±5.2%, constriction, p<0.05). HFI419 had no effect on control aorta or aorta with mild aortic dysfunction. The present study shows that HFI419 prevents acetylcholine mediated vasoconstriction in dysfunctional blood vessels. HFI419 had no effect on normal vasodilation. Our results indicate a therapeutic potential of HFI419 in reducing coronary artery vasospasm.
Topics: Acetylcholine; Animals; Aorta, Abdominal; Cystinyl Aminopeptidase; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Male; Organ Culture Techniques; Rabbits; Vasoconstriction
PubMed: 27936390
DOI: 10.1016/j.biopha.2016.11.142 -
Hypertension (Dallas, Tex. : 1979) Jun 1993Previous in vitro studies indicate that insulin modifies vascular reactivity to different agents. We have previously demonstrated that in normotensive humans...
Previous in vitro studies indicate that insulin modifies vascular reactivity to different agents. We have previously demonstrated that in normotensive humans physiological hyperinsulinemia is associated with an increase of forearm norepinephrine release but does not modify vascular resistance. To explore whether insulin modulates peripheral vasoconstriction induced by reflex sympathetic activation, we studied its effects on forearm hemodynamics (strain-gauge plethysmography) during graded levels of lower body negative pressure (-5, -10, -15, and -20 mm Hg, each for 5 minutes) in normotensive subjects. For this purpose, eight subjects received an intrabrachial artery infusion of regular insulin at a systemically ineffective rate (0.05 milliunits/kg per minute) so that deep-venous insulin levels increased in the experimental forearm from 16.5 +/- 2.9 to 379.6 +/- 30 pmol/L (p < 0.01), whereas arterial insulin levels remained unchanged (from 40.9 +/- 8.6 to 43.1 +/- 7.9 pmol/L, NS). In the control arm, forearm vascular resistance (units) increased from 52.3 +/- 3 to a peak of 78.4 +/- 5 (p < 0.001) during lower body negative pressure. In the insulin-exposed forearm, vascular resistance (46.4 +/- 2 at baseline) remained unchanged during insulin infusion (45.8 +/- 3, NS) and rose to a peak of 54.8 +/- 6 (p < 0.05) during lower body negative pressure. The response of forearm vascular resistance to lower body negative pressure was different in the two forearms (F = 4.506, p < 0.01, repeated-measures analysis of variance with grouping factor). Our results demonstrate that in normotensive subjects local physiological hyperinsulinemia reduces the forearm vasoconstrictive response to reflex sympathetic activation.
Topics: Adult; Brachial Artery; Forearm; Hemodynamics; Humans; Injections, Intra-Arterial; Insulin; Lower Body Negative Pressure; Reflex; Rest; Sympathetic Nervous System; Vasoconstriction
PubMed: 8505085
DOI: 10.1161/01.hyp.21.6.1015 -
European Journal of Pharmacology Feb 1999The role of perivascular calcitonin gene-related peptide (CGRP)-containing nerves in the modulation of adrenergic nerve-mediated vasoconstrictions was studied in the rat...
The role of perivascular calcitonin gene-related peptide (CGRP)-containing nerves in the modulation of adrenergic nerve-mediated vasoconstrictions was studied in the rat perfused mesenteric vascular bed. A frequency-dependent vasoconstriction induced by periarterial nerve stimulation (1-6 Hz) of the bed was significantly potentiated by perfusion of 1 microM CGRP-(8-37) (CGRP receptor antagonist) or to a similar extent after treatment with 500 nM capsaicin. In the preparations treated with capsaicin, CGRP-(8-37) caused a small potentiation of periarterial nerve stimulation-induced vasoconstriction. Exogenous CGRP (0.1-1 nM) concentration-dependently attenuated the augmented vasoconstriction in response to periarterial nerve stimulation after treatment with capsaicin. However, exogenous CGRP (1 nM) did not attenuate the periarterial nerve stimulation-induced vasoconstriction in the bed untreated with capsaicin. These results suggest that endogenous CGRP, which is released from CGRP-containing nerves, suppresses the adrenergic nerve function involved in mechanisms regulating the tone of resistant blood vessels.
Topics: Animals; Calcitonin Gene-Related Peptide; Calcitonin Gene-Related Peptide Receptor Antagonists; Capsaicin; Dose-Response Relationship, Drug; Drug Synergism; Electric Stimulation; In Vitro Techniques; Male; Mesentery; Norepinephrine; Rats; Sympathetic Nervous System; Vasoconstriction; Vasoconstrictor Agents
PubMed: 10078998
DOI: 10.1016/s0014-2999(98)00949-2 -
Journal of Applied Physiology... Jan 1991To characterize the effects of glucose on the pulmonary vascular response to anoxia and hypoxia, isolated ferret lungs were ventilated with 28% O2 and 5% CO2 and...
To characterize the effects of glucose on the pulmonary vascular response to anoxia and hypoxia, isolated ferret lungs were ventilated with 28% O2 and 5% CO2 and perfused at constant flow (100 ml.kg-1.min-1). Perfusate glucose concentrations were allowed to fall spontaneously to less than 1 mM (low glucose) or were controlled at 5-6 mM (normal glucose) or 12-17 mM (high glucose). At 60, 120, and 180 min of perfusion, the inspired O2 tension (PIO2) was reduced to 0, 10, or 30 Torr for 30 min, and vasomotor responses were quantified by continuous measurement of pulmonary arterial pressure. At PIO2 of 0 Torr, the response consisted of an early phase of transient intense vasoconstriction and a late phase of sustained slight vasoconstriction. High glucose markedly potentiated the magnitude of late-phase vasoconstriction with each successive anoxic exposure. This effect was not reproduced in normal glucose lungs and was not caused by a change in perfusate osmolarity, an action on blood cells, or an altered ability of pulmonary vascular smooth muscle to contract. At PIO2 of 10 Torr, high glucose not only potentiated late-phase vasoconstriction but also slowed the onset of early-phase vasoconstriction. At PIO2 of 30 Torr, high glucose had no effect on vasomotor responses, which were characterized by a slowly developing sustained vasoconstriction. Our results suggest that the vascular response of isolated ferret lungs to severe hypoxia consisted of separate early and late phases of vasoconstriction. This biphasic response may have resulted from two distinct vasoconstrictor mechanisms or from modulation of a single vasoconstrictor mechanism by a secondary vasodilator influence.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Animals; Ferrets; Glucose; Hypoxia; In Vitro Techniques; Male; Perfusion; Pulmonary Circulation; Vasoconstriction
PubMed: 2010403
DOI: 10.1152/jappl.1991.70.1.439 -
Microvascular Research Jul 2003Water immersion skin wrinkling tests limb sympathetic vasoconstrictor function. We have recently shown that water immersion wrinkling is accompanied by digit...
Water immersion skin wrinkling tests limb sympathetic vasoconstrictor function. We have recently shown that water immersion wrinkling is accompanied by digit vasoconstriction and postulated that vasoconstriction is the main underlying mechanism. To test this further, we applied vasoconstrictive cream (EMLA) to the distal digit and compared the degree of skin wrinkling and digit blood flow reduction with those after water immersion. In 25 healthy volunteers (6 male, 19 female; mean age, 35 yr) subjected to EMLA and water immersion, both clinical wrinkling scores and reduction in digit blood flow (mean of 2.01 and 2.29 cm/s, respectively) were nearly identical. Control using aqueous cream resulted in minimal skin wrinkling and nonsignificant reduction in digit artery flow (P = 0.170). These data further support that water immersion skin wrinkling is mediated by vasoconstriction. The EMLA cream patch test may develop into a useful screening test for hand sympathetic vasoconstrictor function.
Topics: Adult; Female; Humans; Immersion; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Ointments; Oxidants; Prilocaine; Regional Blood Flow; Skin; Skin Aging; Vasoconstriction; Vasoconstrictor Agents; Water
PubMed: 12826076
DOI: 10.1016/s0026-2862(03)00020-7 -
General Pharmacology Feb 2000Catecholamines induce direct vasoconstriction mediated by postsynaptic alpha-adrenergic receptors (alpha-ARs) of both the alpha(1) and alpha(2) type. To evaluate the...
Catecholamines induce direct vasoconstriction mediated by postsynaptic alpha-adrenergic receptors (alpha-ARs) of both the alpha(1) and alpha(2) type. To evaluate the contribution of each alpha(2)-AR subtype (alpha(2A), alpha(2B), and alpha(2C)) to this function, we used groups of genetically engineered mice deficient for the gene to each one of these subtypes and compared their blood pressure (BP) responses to their wild-type counterparts. Blood pressure responses to a bolus of norepinephrine (NE) were assessed before and after sequential blockade of alpha(1)-ARs with prazosin and alpha(2)-ARs with yohimbine. The first NE bolus elicited a brief 32 to 44 mm Hg BP rise (p < 0.001 from baseline) in all six groups. Prazosin decreased BP by 23 to 33 mm Hg in all groups, establishing a new lower baseline. Repeat NE at that point elicited lesser but still significant (p < 0.001) brief pressor responses between 32% and 45% of the previous BP rise in five of the six groups. Only the alpha(2A)-AR gene knockouts differed, responding instead with a 20-mm Hg fall in BP, a significant change from baseline (p < 0.001) and different from the pressor response of their wild-type counterparts (p < 0.001). The addition of yohimbine produced no further BP change in the five groups, but it did produce a small 7. 5-mm Hg fall (p < 0.05) in the alpha(2A)-AR knockouts. Norepinephrine bolus during concurrent alpha(1) and alpha(2)-AR blockade produced significant (p < 0.001) hypotensive responses in all subgroups, presumably attributable to unopposed stimulation of beta(2)-vascular wall ARs. We conclude that the alpha(2)-AR-mediated vasoconstriction induced by catecholamines is attributable to the alpha(2A)-AR subtype because mice deficient in any one of the other subtypes retained the capacity for normal vasoconstrictive responses. However, the alpha(1)-ARs account for the major part (as much as 68%) of catecholamine-induced vasoconstriction.
Topics: Adrenergic alpha-2 Receptor Antagonists; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Blood Pressure; Male; Mice; Mice, Knockout; Norepinephrine; Prazosin; Receptors, Adrenergic, alpha-2; Vasoconstriction; Vasoconstrictor Agents; Yohimbine
PubMed: 10974417
DOI: 10.1016/s0306-3623(00)00051-3 -
Respiratory Physiology & Neurobiology Dec 2011Injecting hypertonic saline into the lung periphery causes a vagally mediated neural hyperpnea and tachypnea (the excitatory lung reflex, ELR). In the present study, we...
Injecting hypertonic saline into the lung periphery causes a vagally mediated neural hyperpnea and tachypnea (the excitatory lung reflex, ELR). In the present study, we tested the hypothesis that hypertonic saline activates lung afferents mainly by increasing fluid flux from pulmonary vessels into the alveoli. If our hypothesis is correct, reducing perfusion of the vagal sensory region will reduce the fluid flux and attenuate the ELR. In anesthetized, open chest and mechanically ventilated rabbits, using intravital video microscopy, we confirmed that topical KCl (100 mM) constricted sub-pleural blood vessels and limited blood flow significantly, as indicated by a 43.3±9% decrease in arteriolar diameters (p<0.005), sluggish microvascular flow and paleness of alveolar walls. Then, we compared respiratory responses (assessed from phrenic nerve activity) to injections of hypertonic saline (8.1%, 0.1 ml) into the lung periphery before and after locally injecting KCl to limit fluid flux. The respiratory responses were the same with or without vasoconstriction. However, the responses were significantly decreased (from 22±5% to 1±2% for phrenic amplitude and from 75±9% to 13±6% for phrenic burst rate; n=14, p<0.02) after local injection of 2% lidocaine to block sensory endings. Since the ELR was not attenuated by vasoconstriction, increased transvascular fluid flux does not appear to be a major mechanism for hypertonic saline induced ELR.
Topics: Afferent Pathways; Animals; Lung; Male; Rabbits; Respiration; Saline Solution, Hypertonic; Vagus Nerve; Vasoconstriction
PubMed: 21983524
DOI: 10.1016/j.resp.2011.09.014 -
American Journal of Physiology.... Aug 2001Recent evidence indicates that endothelin-1 (ET-1) might be a principal vasoconstrictor in the penis. We report that ET-1 injection into the cavernous sinuses before...
Recent evidence indicates that endothelin-1 (ET-1) might be a principal vasoconstrictor in the penis. We report that ET-1 injection into the cavernous sinuses before erection sharply reduced the magnitude of subsequent erections. Corpus cavernosum pressure-to-mean arterial pressure ratios (CCP/MAP), with maximal ganglionic stimulation, were 0.62 +/- 0.05 before ET-1 injection and 0.31 +/- 0.05 after, indicating that ET-1 acted as a vasoconstrictor. When ET-1 was injected during a maximal neurally induced erection, the ability of ET-1 to attenuate subsequent erections was diminished (CCP/MAP 0.75 +/- 0.02 before ET-1, 0.61 +/- 0.03 after). At submaximal stimulation voltages, injection of ET-1 during erection also attenuated its vasoconstrictive effect. Similarly, when ET-1 was injected during erection induced by intracavernosal injection of the nitric oxide (NO) donor NOR-1, subsequent erections were not significantly suppressed (CCP/MAP 0.53 +/- 0.04 before ET-1, 0.45 +/- 0.04 after). These findings that ET-1-induced vasoconstriction is attenuated during erection are consistent with the hypothesis that NO mediates erection both by initiating pathways that cause smooth muscle relaxation and by inhibiting the vasoconstrictive actions of ET-1.
Topics: Animals; Blood Pressure; Electric Stimulation; Endothelin-1; Humans; Male; Nitric Oxide Donors; Penile Erection; Rats; Vasoconstriction; Vasoconstrictor Agents
PubMed: 11448850
DOI: 10.1152/ajpregu.2001.281.2.R476 -
European Heart Journal Feb 2003
Topics: Humans; Hypertension, Pulmonary; Vasoconstriction; Vasodilation; Vasodilator Agents
PubMed: 12581676
DOI: 10.1016/s0195-668x(02)00753-4