Differential effects of carbachol on cytosolic calcium levels in vascular endothelium and smooth muscle.
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.
Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
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Sato
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Ozaki
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Karaki
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology*; D003600:Cytosol / Q000737:chemistry*; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects
D009569:Nitric Oxide; D006632:Histamine; D002217:Carbachol; D002118:Calcium; D009638:Norepinephrine