EFFECTS OF ENDOTHELIN-1 IN ISOLATED PERFUSED RAT-HEART

被引:69
作者
NEUBAUER, S
ERTL, G
HAAS, U
PULZER, F
KOCHSIEK, K
机构
[1] Medizinische Univ.-Klinik, 87 Wurzburg
关键词
Captopril; Coronary flow; Endothelin-1; Indomethacin; Isolated rat heart;
D O I
10.1097/00005344-199007000-00001
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We examined the effects of the vasoconstrictor peptide endothelin-1 in the isolated heart and defined interactions of endothelin-1 with other hormone systems. Isolated isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. First, the effect of a single bolus of endothelin-1 (4-400 pmol) was followed for 90 min. The effect of high dosages (40 and 400 pmol) of endothelin-1 on coronary flow was biphasic, with an early vasodilator and a late vasoconstrictor component that was irreversible. Second, cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04-400 pmol. Coronary flow declined with increasing dosages and was almost abolished at 400 pmol. Neither α- nor β-blocking agents (phentolamine and propranolol) nor the Ca2+-channel blocker nifedipine altered the effect of endothelin-1, but prostaglandin synthesis inhibition by indomethacin significantly augmented vasoconstriction by endothelin-1. Angiotensin-converting enzyme (ACE) inhibition by captopril antagonized endothelin-1-dependent vasoconstriction to a small extent at 400 pmol. Coronary constriction due to endothelin-1 could not be reversed by nitroglycerin. We conclude that in isolated rat heart endothelin-1 causes marked and longlasting coronary constriction. The effect is not influenced by sympathetic and Ca2+-channel blockade, is enhanced by prostaglandin synthesis inhibition, and is reduced by ACE inhibition.
引用
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页码:1 / 8
页数:8
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