ROLE OF INTRACELLULAR AND EXTRACELLULAR CALCIUM IN ALPHA(1)-ADRENOCEPTOR-MEDIATED VASOCONSTRICTION IN THE RAT PERFUSED HINDQUARTERS

The influence of the calcium channel antagonists, felodipine and cadmi um, as well as of the putative phospholipase C inhibitor, 2-nitro-4-ca rboxyphenyl N,N-diphenylcarbamate (NCDC), on the vasoconstrictor actio ns of methoxamine in the rat perfused hindquarters was examined. Chang es in perfusion pressure following bolus administration of methoxamine were monitored under constant flow. Methoxamine produced a dose-depen dent increase in perfusion pressure of the hindquarters. Inclusion of cadmium (30 mu M) in the physiological salt solution significantly red uced the maximum response, without significantly altering the ED(50) o r the Hill coefficient of the dose-response curve to methoxamine. Addi tion of felodipine (0.3 and 1 mu M) in the physiological salt solution inhibited the vasoconstrictor actions of methoxamine. The dose-respon se curve to methoxamine was displaced to the right, with significant i ncreases in ED(50) and Hill coefficient, and the maximum response was significantly reduced. The vasoconstrictor action of methoxamine was a lso inhibited by NCDC (10 mu M). The maximum response decreased and th e Hill coefficient increased significantly, while the ED(50) was not s ignificantly altered. The presence of NCDC, together with either felod ipine or cadmium, did not result in a further additive inhibition of t he methoxamine-induced vasoconstriction. The inhibitory effects of fel odipine and cadmium were partially reduced in the presence of NCDC. It is concluded that, in the rat perfused hindquarters, the vasoconstric tor actions of methoxamine depend on both intracellular and extracellu lar calcium ions. Calcium influx occurs, in part, via the felodipine-s ensitive calcium channels. It is also apparent that NCDC interfered wi th the inhibitory actions of cadmium and felodipine.