Abstract
Effects of norepinephrine (NE), carbachol (CCh) and histamine (HIS) on vascular tone and the endothelial and smooth muscle cytosolic C++ levels ([Ca++]i) were examined in rat aorta. The fura-2-Ca++ fluorescence emitted from endothelial and smooth muscle cells was detected at the endothelial surface. In the aorta with endothelium, NE increased both [Ca++]i and muscle tension whereas CCh slightly relaxed the muscle and increased [Ca++]i. The CCh-stimulated [Ca++]i was partially inhibited by verapamil. Addition of CCh to the NE-stimulated aorta relaxed the muscle with additional increase in [Ca++]i and positive correlation was obtained between the increase in [Ca++]i and relaxation. In the aorta without endothelium, NE increased both [Ca++]i and tension although CCh was ineffective. When endothelium was removed only from a small area from where the fura-2-Ca++ fluorescence was detected, CCh relaxed the muscle without changing [Ca++]i. In this preparation, NE increased both [Ca++]i and muscle tension and sequential addition of CCh relaxed the muscle with a small decrease in [Ca++]i, suggesting that Ca++ sensitivity of contractile elements is decreased. In Ca+(+)-free solution, CCh induced a transient increase in [Ca++]i and a decrease in muscle tension only in the presence of endothelium. HIS showed similar effects as CCh. By contrast, sodium nitroprusside decreased [Ca++]i and relaxed the muscle in NE-stimulated aorta with or without endothelium. These results suggest that CCh and HIS increase [Ca++]i in the endothelial cells which regulates the synthesis and/or release of endothelium-derived relaxing factor. Endothelium-derived relaxing factor may decrease [Ca++]i in the smooth muscle cells and also decrease Ca++ sensitivity of contractile elements resulting in vasodilatation.
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