| Verapamil: a selective antagonist of constrictor substances in dog coronary artery: implications for variant angina. | |
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MedLine Citation:
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PMID: 6956474 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. Canine circumflex coronary artery ring segments were contracted in vitro by ergometrine, serotonin, phenylephrine, noradrenaline (with propranolol) and a thromboxane A2 analogue, U46619. 2. Ergometrine was classified as a serotonin agonist since concentration-response curves were competitively inhibited by methysergide but not by alpha-adrenoceptor antagonists. 3. Glyceryl trinitrate (IC50 18.6 nmol/l) relaxed the coronary rings precontracted with serotonin, phenylephrine or U46619. In contrast (+/-)-verapamil (0.1-10 mumol/l) was more effective against serotonin than phenylephrine or noradrenaline and was almost inactive against U46619. 4. In a blood perfused left anterior descending coronary artery preparation external diameter was measured by sonomicrometry. Serotonin, U46619 and ergometrine infusions (i.a.) decreased diameter by up to 18% without causing spasm (zero lumen diameter). Lowering the perfusion pressure from 90 to 60 mmHg increased the fall in diameter during serotonin infusions. 5. The negative inotropic potency of verapamil against noradrenaline induced beta-adrenergic stimulation in guinea-pig left atria was compared with the vasodilator potency of verapamil in noradrenaline constricted dog coronary artery rings. Verapamil was eighteen times more potent in cardiac muscle than in coronary smooth muscle. 6. This apparent tissue selectivity of verapamil was confirmed in anaesthetized dogs where plasma concentrations of verapamil 50-150 ng/ml (in the therapeutic range) lowered blood pressure and heart rate and increased P-R interval without greatly reducing the constrictor response to serotonin in the coronary artery. 7. These studies suggest that inhibition of constrictor responses in large coronary vessels may not be an important site of action of verapamil in patients with variant angina. |
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Authors:
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J A Angus; R M Brazenor; M A Le Duc |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and experimental pharmacology & physiology. Supplement Volume: 6 ISSN: 0143-9294 ISO Abbreviation: Clin Exp Pharmacol Physiol Suppl Publication Date: 1982 |
Date Detail:
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Created Date: 1982-12-02 Completed Date: 1982-12-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7611484 Medline TA: Clin Exp Pharmacol Physiol Suppl Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 15-28 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angina Pectoris, Variant
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drug therapy Animals Blood Pressure / drug effects Calcium Channel Blockers / pharmacology*, therapeutic use Coronary Vessels / drug effects*, physiology Dogs Dose-Response Relationship, Drug Ergonovine / pharmacology Female Guinea Pigs Heart Atria / drug effects Male Muscle, Smooth, Vascular / drug effects Norepinephrine / antagonists & inhibitors Perfusion Serotonin / pharmacology Stimulation, Chemical Vasodilator Agents / pharmacology*, therapeutic use Verapamil / pharmacology*, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channel Blockers; 0/Vasodilator Agents; 50-67-9/Serotonin; 51-41-2/Norepinephrine; 52-53-9/Verapamil; 60-79-7/Ergonovine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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