Differential effects of calcium channel blockade and intracellular calcium antagonism on endothelium-dependent responses of the rat aorta to drugs.
The actions of many vasoactive drugs are mediated through, or modified by, the endothelium-derived relaxing (EDRF) and constricting (EDCF) factors. While EDRF appears to be nitric oxide, EDCF is a peptide or cyclooxygenase product. Using verapamil (a calcium channel blocker), propyl methylenedioxyindene (pr-MDI; an intracellular calcium antagonist), and sodium nitroprusside (which liberates nitric oxide from its molecular structure) as EDRF-independent pharmacological probes in rat aortic rings with and without endothelium, we attempted to provide additional insight into the role of extracellular [( Ca]o) and intracellular [( Ca]i) calcium in EDRF and EDCF release and action, and to explain some mechanisms underlying the modulatory effects of these endothelial factors on the actions of vasoactive drugs. The findings suggest that (1) the [Ca]o required for evoked EDRF release does not enter endothelial cells through verapamil-sensitive calcium channels; (2) mobilization of endoplasmic reticular [Ca]i by [Ca]o entering the endothelial cell may be the trigger for evoked EDRF release; (3) spontaneous release of EDRF appears to depend more on mobilization of [Ca]i than on influx of [Ca]o; (4) the action of EDRF on smooth muscle either does not require Ca or does not involve the mobilization of [Ca]i by [Ca]o; (5) Both EDRF and EDCF can modulate the actions of vasoactive drugs; (6) the EDCF of the rat aorta is not a cyclooxygenase product, and (7) the action of EDCF on vascular smooth muscle, and possibly its release from endothelial cells, are Ca-dependent.
Olah
M E
ME
Division of Pharmacology, Ohio State University, Columbus.
Rahwan
R G
RG
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001685:Biological Factors / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D001685:Biological Factors; D002121:Calcium Channel Blockers; D009569:Nitric Oxide; D014700:Verapamil; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine