| Coronary arterial lesions in dogs treated with an endothelin receptor antagonist. | |
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MedLine Citation:
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PMID: 9595490 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Structurally and pharmacologically diverse vasodilators are known to lower blood pressure, increase heart rate, and produce acute injury to right coronary arteries in the dog. Administration of low concentrations of endothelin-1 (ET-1) to anesthetized dogs causes coronary vasoconstriction and reductions in coronary blood flow. Therefore, pharmacologic blockade of endothelin receptors (ETA and ETB) with the mixed ET receptor antagonist SB 209670 could lead to coronary vasodilatation. In toxicology studies, continuous administration of SB 209670 to dogs for 5 days at 50 micrograms/kg/min was associated with minor but sustained increases in heart rate (10-30 beats/min), slight decreases in mean arterial pressure (10-15 mm Hg), and medial hemorrhage and necrosis of extramural coronary arteries in the right atria. Doses of 10 micrograms/kg/min had no effect. The lesions in the right atrium were associated with the highest density of ET receptors, approximately 470 fmol/mg compared to 170-200 fmol/mg in the ventricles and septum. Because changes in systemic cardiovascular parameters are minimal, the coronary arterial lesion is most likely due to a local vasodilatory effect in the coronary bed. |
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Authors:
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C Louden; P Nambi; C Branch; K Gossett; M Pullen; S Eustis; H A Solleveld |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 31 Suppl 1 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1998 |
Date Detail:
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Created Date: 1998-07-17 Completed Date: 1998-07-17 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: S384-5 Citation Subset: IM |
Affiliation:
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Department of Toxicology-US, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Coronary Disease / chemically induced*, physiopathology Dogs Female Indans / metabolism, toxicity* Male Receptors, Endothelin / antagonists & inhibitors*, metabolism Vasodilation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Indans; 0/Receptors, Endothelin; 157659-79-5/SB 209670 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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