Removal of endothelial function in coronary resistance vessels by saponin

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Abstract
Studies of the role of the endothelium in coronary resistance vessels are limited to investigations of endothelium-derived relaxing factor mediated effects using various blocking agents. Endothelium removal as an alternative approach, is restricted to larger epicardial vessels. This study demonstrates the effect of endothelial damage by saponin on coronary resistance vessels remaining intact within the heart. In an isolated perfused guinea pig heart a saponin-containing solution (50 μg/ml) was infused over 2 min to damage specifically the endothelium. Increases of coronary flow in response to carbachol, histamine, and serotonin were completely blocked and reversed to decreases. Angiotensin-I-induced vasoconstriction was attenuated, whereas angiotensin-II-induced vasoconstriction remained unchanged. Vasodilatory response to sodium-nitroprusside was not attenuated by saponin-treatment. In contrast inhibition of endothelium derived relaxing factor by gossypol inhibited carbachol-induced vasodilation but did not result in vasoconstriction. Electron microscopic examination ensured that while the endothelium was destroyed by saponin-treatment the vascular smooth muscle was left intact. Our data indicate a regulating influence of the vascular endothelium on coronary resistance vessels which can be totally eliminated by saponin-treatment.