title: Role of intracellular and extracellular calcium in alpha 1-adrenoceptor-mediated vasoconstriction in the rat perfused hindquarters.
abstract: The influence of the calcium channel antagonists, felodipine and cadmium, as well as of the putative phospholipase C inhibitor, 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate (NCDC), on the vasoconstrictor actions of methoxamine in the rat perfused hindquarters was examined. Changes in perfusion pressure following bolus administration of methoxamine were monitored under constant flow. Methoxamine produced a dose-dependent increase in perfusion pressure of the hindquarters. Inclusion of cadmium (30 microM) in the physiological salt solution significantly reduced the maximum response, without significantly altering the ED50 or the Hill coefficient of the dose-response curve to methoxamine. Addition of felodipine (0.3 and 1 microM) in the physiological salt solution inhibited the vasoconstrictor actions of methoxamine. The dose-response curve to methoxamine was displaced to the right, with significant increases in ED50 and Hill coefficient, and the maximum response was significantly reduced. The vasoconstrictor action of methoxamine was also inhibited by NCDC (10 microM). The maximum response decreased and the Hill coefficient increased significantly, while the ED50 was not significantly altered. The presence of NCDC, together with either felodipine or cadmium, did not result in a further additive inhibition of the methoxamine-induced vasoconstriction. The inhibitory effects of felodipine and cadmium were partially reduced in the presence of NCDC. It is concluded that, in the rat perfused hindquarters, the vasoconstrictor actions of methoxamine depend on both intracellular and extracellular calcium ions. Calcium influx occurs, in part, via the felodipine-sensitive calcium channels. It is also apparent that NCDC interfered with the inhibitory actions of cadmium and felodipine.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Tabrizchi
mesh_terms: D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D015736:Felodipine / Q000494:pharmacology*; D008297:Male; D008729:Methoxamine / Q000633:toxicity; D010477:Perfusion; D048448:Phenylcarbamates; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D002219:Carbamates; D002712:Chlorides; D048448:Phenylcarbamates; D018340:Receptors, Adrenergic, alpha-1; D002104:Cadmium; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; D010738:Type C Phospholipases; D008729:Methoxamine; D019256:Cadmium Chloride; D015736:Felodipine; D011188:Potassium; D002118:Calcium