Myocardial ischaemia induced by endothelin in the intact rabbit: angiographic analysis

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Abstract
Study objective – The aim was to clarify the effects of endothelin on coronary vasculature in the intact rabbit by coronary angiographic examination. Design – By selective coronary angiography bolus injections of various amounts of endothelin (0.01-1 nmol) were given into the right coronary artery of anaesthetised rabbits. The preventive effects of nifedipine on endothelin induced myocardial ischaemia were examined. Subjects – Adult male Japanese white rabbits (2.7-3.5 kg, n=29) were used for in vivo and in vitro studies. Measurements and main results – Intracoronary administration of 0.1 nmol endothelin led to the delayed filling of contrast medium into the distal coronary artery and the sustained retention of contrast medium in both large and small coronary arteries, associated with distinct ST elevation in leads II, III and aVF on the electrocardiogram. However, endothelin produced no evident constriction at any site in the large epicardial coronary arteries. Intracoronary administration of glyceryl trinitrate (50 μg) or nifedipine (5 μg) failed to reverse myocardial ischaemic changes induced by endothelin. Pretreatment with intravenous administration of nifedipine (3 μg·kg−1) partially inhibited the endothelin induced vasoconstrictor effect on small coronary arteries and subsequent ischaemic changes. In isolated coronary arterial preparation, endothelin produced long lasting contraction in a dose dependent manner [ED50=3.7 (SEM 1.8) nM]. Pretreatment with nifedipine inhibited the maximum contraction induced by endothelin, but did not affect the threshold dose or the half maximal effective dose (ED50). Endothelin (0.1 μM) per se did not produce aggregatory responses of rabbit platelets. Conclusions – Endothelin induced myocardial ischaemia cannot be ascribed to vasospastic constriction of large coronary arteries nor to platelet thrombi, but diffuse constriction of small coronary arteries occurs in the intact rabbit.