| Coronary vasoconstriction by endothelin-1 in anesthetized goats: role of endothelin receptors, nitric oxide and prostanoids. | |
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MedLine Citation:
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PMID: 8960882 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The role of endothelin ETA and ETB receptors as well as of nitric oxide (NO) and prostanoids in the effects of endothelin-1 on the coronary circulation was studied in anesthetized goats. Where blood flow in the left circumflex coronary artery (coronary blood flow) (electromagnetically measured), systemic arterial pressure, left ventricle pressure and d P/dt, and heart rate were recorded. Endothelin-1 (0.01-0.3 nmol), intracoronarily injected, produced marked, dose-dependent reductions in basal coronary blood flow, ranging from 5% for 0.01 nmol to 75% for 0.3 nmol; 0.1 and 0.3 nmol endothelin-1 also reduced systolic ventricle pressure and dP/dt. The effects of endothelin-1 on coronary blood flow were diminished during intracoronary infusion of BQ-123 (cyclo-(D-Asp-Pro-D-Val-Leu-D-Trp). specific antagonist for endothelin ETA receptors. 2-16 nmol/min) in a dose-dependent way, but not during the infusion of BQ-788 (N-[N-[N-[(2.6-dimethyl-1-piperidinyl)carbonyl]-4-methyl-1-leucyl]-1- (methoxycarbonyl)-D-tryptophyl]-D-norleucine monosodium, specific antagonist for endothelin ETB receptors. 2-4 nmol/min). IRL 1620 (Suc-[Glu9, Ala11.15]endothelin-1-(8-21), specific agonist for endothelin ETB receptors. 0.01-0.3 nmol), intracoronarily injected. slightly reduced basal coronary blood flow only when 0.1 and 0.3 nmol were applied (maximal reduction about 25%); 0.3 nmol IRL 1620 also reduced systolic ventricle pressure and dP/dt. The effects of IRL 1620 were not modified by BQ-123 or BQ-788. NG-nitro-1-arginine methyl ester (L-NAME, inhibitor of NO synthesis, 47 mg/kg by i.v. route) reduced resting coronary blood flow by 10% and increased mean systemic arterial pressure and systolic ventricle pressure by 22 and 20%. respectively, without changing systolic ventricle dP/dt and heart rate. With L-NAME, the reductions of coronary blood flow by endothelin-1 were potentiated (P < 0.05), and those by IRL 1620 were not changed (P > 0.05). Meclofenamate (cyclooxygenase inhibitor, 4-6 mg/kg by i.v. route) modified neither the basal values of hemodynamic variables nor the coronary effects of endothelin-1 and IRL 1620. Therefore, endothelin-1 produces marked coronary vasoconstriction, which may be mediated by endothelin ETA receptors, with no participation of endothelin ETB receptors. NO, but not prostanoids, may produce a basal coronary vasodilator tone and may inhibit endothelin-1-induced coronary vasoconstriction. Also, it is suggested that the coronary vasoconstriction by endothelin-1 may impair cardiac performance due to heart ischemia. |
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Authors:
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J L García; N Fernández; A L García-Villalón; L Monge; B Gómez; G Diéguez |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of pharmacology Volume: 315 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 1996 Nov |
Date Detail:
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Created Date: 1997-04-03 Completed Date: 1997-04-03 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: NETHERLANDS |
Other Details:
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Languages: eng Pagination: 179-86 Citation Subset: IM |
Affiliation:
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Deparatmento de Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anesthesia, Intravenous* Anesthetics, Dissociative* Animals Coronary Circulation / drug effects Endothelin-1 / pharmacology* Endothelins / pharmacology Female Goats Hemodynamics / drug effects Ketamine* Nitric Oxide / physiology* Oligopeptides / pharmacology Peptide Fragments / pharmacology Peptides, Cyclic / pharmacology Piperidines / pharmacology Prostaglandins / physiology* Receptors, Endothelin / drug effects, physiology* Vasoconstriction / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Dissociative; 0/BQ 788; 0/Endothelin-1; 0/Endothelins; 0/Oligopeptides; 0/Peptide Fragments; 0/Peptides, Cyclic; 0/Piperidines; 0/Prostaglandins; 0/Receptors, Endothelin; 10102-43-9/Nitric Oxide; 136553-81-6/cyclo(Trp-Asp-Pro-Val-Leu); 142569-99-1/IRL 1620; 6740-88-1/Ketamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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