Different susceptibility of vasodilator nerve, endothelium and smooth muscle functions to Ca++ antagonists in cerebral arteries.
Effects of selective (nicardipine) and nonselective (Cd++) Ca++ channel antagonists on the responses of isolated dog cerebral arteries to vasodilator nerve stimulation, substance P, serotonin and prostaglandin F2 alpha were investigated; the relaxation caused by the nerve stimulation and the peptide is mediated by NO, possibly from the nerve and endothelium, respectively. Relaxant responses to nerve stimulation by electrical pulses and nicotine in the endothelium-denuded arteries were attenuated by Cd++, but not influenced by nicardipine; the concentrations of these antagonists were sufficient to suppress contractions caused by prostaglandin F2 alpha and serotonin to a similar extent. Increase in cyclic GMP by nicotine was also suppressed solely by Cd++. In the endothelium-intact arteries treated with indomethacin, relaxations induced by substance P were not affected by nicardipine, but were significantly attenuated by Cd++. The peptide-induced increase in cyclic GMP was suppressed by Cd++, but not by nicardipine. It is concluded that functional properties of the Ca++ channel responsible for increasing cytosolic Ca++ in the nerve and endothelium for the synthesis and release of nitric oxide or endothelium-derived relaxing factor differ from those of the channel in smooth muscle. Because Ca++ is a prerequisite for the synthesis of NO, smooth muscle does not appear to be the site of production of NO that transmits vasodilator information from the nerve or endothelium to cerebroarterial smooth muscle.
Toda
N
N
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Okamura
T
T
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009411:Nerve Endings / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology
D002104:Cadmium; D009569:Nitric Oxide; D012701:Serotonin; D009538:Nicotine; D009529:Nicardipine