Additional Hypotensive Effect of Endothelin-1 Receptor Antagonism in Hypertensive Dogs Under Angiotensin-Converting Enzyme Inhibition
| Autor: | Jean-Marie Ketelslegers, André A. Charlier, PE Massart, Henri Van Mechelen, Olivier Laloux, Jean-Paul Clozel, Julian Donckier, Dominique Hodeige, Guy R. Heyndrickx |
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| Rok vydání: | 1997 |
| Předmět: |
Endothelin Receptor Antagonists
medicine.medical_specialty Enalaprilat Hemodynamics Angiotensin-Converting Enzyme Inhibitors Blood Pressure Pharmacology Dogs Bolus (medicine) Physiology (medical) Internal medicine Animals Medicine Antihypertensive Agents Sulfonamides Dose-Response Relationship Drug Endothelin-1 biology business.industry Bosentan Angiotensin-converting enzyme Blood pressure Endocrinology Hypertension ACE inhibitor biology.protein Vascular Resistance Cardiology and Cardiovascular Medicine business Endothelin receptor medicine.drug |
| Zdroj: | Circulation. 96:1250-1256 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Background Endothelin-1 (ET-1) may play a role in hypertension. ET-1 receptor antagonism by bosentan lowers blood pressure in hypertension. We evaluated whether the effect of bosentan is still observed under ACE inhibitors (ACEI). Methods and Results Thirty anesthetized and 18 conscious hypertensive dogs were studied randomly. Anesthetized dogs were divided into 4 groups: group 1 received cumulative doses of bosentan (bolus+30-minute infusion: 0.1 mg/kg+0.23 mg/kg per hour to 3 mg/kg+7 mg/kg per hour); group 2, the same dose-responses after 1 mg/kg enalaprilat; group 3, the vehicle after enalaprilat; and group 4, the dose responses to bosentan followed by enalaprilat. The conscious dogs were divided into 3 groups: group 5 received 2 cumulative doses of bosentan; group 6, the vehicle; and group 7, enalaprilat alone. In groups 1 and 2, bosentan produced dose-related decreases ( P =.0001) in left ventricular systolic pressure and mean aortic pressure (AOP). In group 1, bosentan decreased mean AOP by 22%. In group 2, enalaprilat decreased mean AOP by 25% (from 173±26 to 130±25 mm Hg; P P P P Conclusions Bosentan produces an additional hypotensive effect to that of ACEI, which opens new therapeutic perspectives. |
| Databáze: | OpenAIRE |
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