0000000000136176
AUTHOR
José A. Alabadí
Modulatory Role of Endothelial and Nonendothelial Nitric Oxide in 5-Hydroxytryptamine-induced Contraction in Cerebral Arteries after Subarachnoid Hemorrhage
OBJECTIVE : Endothelial dysfunction is claimed to play a role in the pathogenesis of delayed cerebral vasospasm after subarachnoid hemorrhage (SAH). We have examined the effect of experimental SAH on the modulatory action of endothelial and nonendothelial nitric oxide (NO) in the contractile response of goat middle cerebral artery to 5-hydroxytryptamine (5-HT). METHODS : We compared the 5-HT-induced contractile responses of cerebral arteries from control goats and from goats with SAH that had been experimentally induced 3 days earlier by delivery of autologous arterial blood into the subarachnoid space. Contractile responses were examined by recording the isometric tension in isolated cereb…
Changes in the cerebrovascular effects of endothelin-1 and nicardipine after experimental subarachnoid hemorrhage.
The role of endothelium-related factors in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH) has gained interest since the discovery of endothelin-1 (ET-1). We have examined, before and after SAH, the responsiveness of the cerebrovascular bed of the goat to ET-1, the sources of Ca2+ in ET-1-induced responses, and the ability of the Ca2+ entry blocker nicardipine to counteract them. Before SAH, injection of ET-1 into the cerebral circulation increased cerebrovascular resistance, thereby producing dose-dependent reductions in cerebral blood flow (CBF), which were prevented by nicardipine. In isolated middle cerebral arteries, ET-1 induced concentration-dependent contr…
Impairment of the modulatory role of nitric oxide on the endothelin-1-elicited contraction of cerebral arteries: a pathogenetic factor in cerebral vasospasm after subarachnoid hemorrhage?
OBJECTIVE: Nitric oxide (NO) and endothelin-1 (ET-1) are two endothelium-derived factors probably involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). Our aim was twofold, i.e., to ascertain whether endothelial and nonendothelial NO modulates the contractile response of cerebral arteries to ET-1 and to analyze whether this relationship might be impaired after experimental SAH. METHODS: Rings of middle cerebral artery from goats in the control group and from goats with SAH were set up for isometric tension recordings. SAH was induced 3 days before the experiments by infusion of 10 ml of autologous arterial blood through a catheter previously inserted into t…
Analysis of Rabbit Vascular Responses to DBI, an Ingol Derivative Isolated from Euphorbia canariensis
Abstract We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI), an ingol derivative isolated from E. canariensis, on isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to DBI (10−8 - 3 × 10−5 m) were obtained cumulatively in both arteries at resting tension and active tone (KC1, 50 mm). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca2+-free medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10−4 m) inhibited the DBI-induced contraction both in basilar and in carotid arteries. Calmidazolium (10−4 m) inhibited the maximum contraction of …
Direct and neuromodulatory effects of histamine on isolated goat cerebral arteries.
1. The effects of histamine on isolated goat middle cerebral artery were examined using two experimental approaches: recording of isometric tension and measurement of [3H]-noradrenaline efflux. 2. Cumulative addition of histamine (10(-7)-3 x 10(-2)M) and 2-pyridylethylamine (2-PEA, 10(-6)-3 x 10(-2)M) produced concentration-dependent contractile responses. Preincubation with diphenhydramine (10(-7), 10(-6)M) or cimetidine (10(-7), 10(-6)M) competitively inhibited the histamine-induced contractile response. 3. Endothelium denudation enhanced the contractile effects of histamine. 4. Transmural electrical stimulation elicited contractions which were enhanced by histamine (10(-7)M), 2-PEA (10(-…
Effects of Ca2+ entry blockers on CaCl2-, KCl- and noradrenaline-induced contractions of goat cerebral arteries
Abstract The effects of three Ca 2+ entry blockers, nicardipine, nimodipine and verapamil, on CaCl 2 -, KCl- and noradrenaline-induced contractions were examined in isolated goat middle cerebral artery. The relationship between the effects of Ca 2+ entry blockers and the extracellular Ca 2+ dependence of the contractions was also examined. In ‘nominally’ Ca 2+ -free medium, addition of CaCl 2 induced concentration-dependent contractions of previously depolarized arteries. Withdrawal of Ca 2+ from the extracellular medium caused strong inhibition of the KCl- and noradrenaline-induced arterial contractions. Addition of EGTA to the Ca 2+ -free medium almost abolished the noradrenaline-response…
Diabetes potentiates acetylcholine-induced relaxation in rabbit renal arteries.
Abstract The response of rabbit renal arteries to acetylcholine and its endothelial modulation in diabetes were investigated. Acetylcholine induced concentration-related endothelium-dependent relaxation of renal arteries that was significantly more potent in diabetic rabbits than in control rabbits. Pretreatment with NG-nitro- l -arginine ( l -NOArg), indomethacin, or l -NOArg plus indomethacin induced partial inhibition of acetylcholine-induced relaxation. Inhibition induced by l -NOArg plus indomethacin was significantly higher in arteries from diabetic rabbits than in arteries from control rabbits. In renal arteries depolarised with KCl 30 mM and incubated with l -NOArg plus indomethacin…
Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1
The influence of diabetes on regulatory mechanisms and specific receptors implicated in the contractile response of isolated rabbit carotid arteries to endothelin-1 was examined. Endothelin-1 induced a concentration-dependent contraction that was greater in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal or N(G)-nitro-L-arginine enhanced contractions in response to endothelin-1 only in control arteries, without modifying the endothelin-1 response in diabetic arteries. Indomethacin, furegrelate (thromboxane A(2) inhibitor), or cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123; endothelin ET(A) receptor antagonist) inhibited the contractions in response to en…
Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery
The influence of alloxan-induced diabetes on the reactivity of rabbit basilar artery to endothelin-1 was examined. Endothelin-1 induced concentration-dependent contraction of basilar arteries that was higher in diabetic than in control rabbits. Endothelium removal produced a higher enhancement of the endothelin-1-induced contraction in control than in diabetic rabbits. N(G)-nitro-L-arginine (L-NOArg) enhanced the maximal contraction induced by endothelin-1 in control rabbits and potentiated this response in diabetic rabbits. Endothelin ETA receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), inhibited endothelin-1-induced contraction in both rabbit groups. Endothelin ETB receptor…
Changes in the adrenergic mechanisms of cerebral arteries after subarachnoid hemorrhage in goats.
We have examined the effects of experimental subarachnoid hemorrhage (SAH), induced by delivering autologous blood into the subarachnoid space, on the adrenergic mechanisms of the goat cerebrovascular bed. To achieve this, the response to noradrenaline was recorded both in vivo, by measuring cerebral blood flow in unanesthetized animals, and in vitro, by recording isometric tension in isolated cerebral arteries. In addition, we checked the function of adrenergic innervation by measuring the tritium efflux evoked by electrical stimulation in cerebral arteries preloaded with [3H]-noradrenaline, and we examined this innervation by using both fluorescent and electron transmission microscopy. Al…
Heterogeneity of P2-Purinoceptors in Brain Circulation
The existence of P2-purinoceptors in the cerebrovascular bed was examined by testing the effects of ATP and its stable analog, α,β-methylene-ATP, on CBF in the unanesthetized goat as well as on isometric tension in isolated goat middle cerebral artery. When injected directly into the cerebral circulation, ATP increased and α,β-methylene-ATP decreased CBF. Indomethacin did not modify either of these effects. The vasoconstrictor action of α,β-methylene-ATP was reduced by nicardipine. “In vitro,” both ATP and α,β-methylene-ATP contracted the cerebral arteries at resting tone, but the analog was more potent than ATP. Repeated application of α,β-methylene-ATP as well as indomethacin significant…
Experimental diabetes induces hyperreactivity of rabbit renal artery to 5-hydroxytryptamine.
Abstract The influence of diabetes on the response of isolated rabbit renal arteries to 5-hydroxytryptamine (5-HT) was examined. 5-HT induced a concentration-related contraction that was higher in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal did not significantly modify 5-HT contractions in arteries from control rabbits but enhanced the response to 5-HT in arteries from diabetic rabbits. Incubation with N G -nitro- l -arginine ( l -NA) enhanced contractions to 5-HT in arteries from control and diabetic rabbits. In arteries with endothelium, this l -NA enhancement was lower in diabetic rabbits than in control rabbits. In arteries without endotheli…
Diabetes-induced changes in endothelial mechanisms implicated in rabbit carotid arterial response to 5-hydroxytryptamine
Abstract The influence of diabetes on endothelial mechanisms implicated in the response of isolated rabbit carotid arteries to 5-hydroxytryptamine (5- HT ) was studied. 5-HT induced a concentration–dependent contraction that was potentiated in arteries from diabetic rabbits with respect to that in arteries from control rabbits. Endothelium removal potentiated 5-HT contractions in arteries from both control and diabetic rabbits but increased the maximum effect only in arteries from diabetic rabbits. Incubation of arterial segments with N G -nitro- l -arginine ( l- NA) enhanced the contractile response to 5-HT. This l -NA enhancement was greater in arteries from diabetic rabbits than in arter…
Contribution of endothelin receptors and cyclooxygenase-derivatives to the altered response of the rabbit renal artery to endothelin-1 in diabetes
Abstract The influence of diabetes on regulatory mechanisms and specific receptors implicated in the response of isolated rabbit renal artery to endothelin-1 was examined. Endothelin-1 induced a concentration-dependent contraction that was less potent in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal or NG-nitro- l -arginine (L-NOARG) enhanced contractions to endothelin-1 either in control and diabetic arteries. Indomethacin inhibited endothelin-1-induced response in control arteries, but enhanced it in diabetic arteries. In contrast to that observed in rubbed and in L-NOARG treated arteries, in the presence of indomethacin the contractile action o…
Perivascular nerve fiber α-synuclein regulates contractility of mouse aorta: A link to autonomic dysfunction in Parkinson's disease
Parkinson's disease and other neurodegenerative disorders associated to changes in alpha-synuclein often result in autonomic dysfunction, most of the time accompanied by abundant expression of this synaptic protein in peripheral autonomic neurons. Given that expression of alpha-synuclein in vascular elements has been previously reported, the present study was undertaken to determine whether alpha-synuclein directly participates in the regulation of vascular responsiveness. We detected by immunohistochemistry perivascular nerve fibers containing alpha-synuclein in the aorta of mice while aortic endothelial cells and muscular fibers themselves did not exhibit detectable levels of this protein…
Comparison of the contractile effects of endothelin-1 and sarafotoxin S6b in goat isolated cerebral arteries
1. The effects of endothelium-derived endothelin-1 and snake venom-derived sarafotoxin S6b, peptides with striking structural and functional similarities, were examined and compared in isolated middle cerebral arteries of goats. 2. Endothelin-1 and sarafotoxin S6b contracted cerebral arteries in a concentration-dependent manner. The potency of endothelin-1 (EC50 = 4.9 (3.9-6.2) x 10(-10) M) was about ten times higher than that of sarafotoxin S6b (EC50 = 5.5 (4.4-6.9) x 10(-9) M). The tension returned to basal values after repeated washings and contraction with endothelin-1 could be reproduced. Endothelin-1 and sarafotoxin S6b induced further contraction in arteries precontracted with prosta…