NIFEDIPINE INHIBITS ADRENAL BUT NOT CIRCULATING CATECHOLAMINE RESPONSE TO NICOTINIC STIMULATION IN DOGS

We investigated whether dihydropyridine-sensitive L-type Ca2+ channels are implicated in adrenal and sympathetic neural catecholamine releas e in response to nicotinic stimulation by 1,1-dimethyl-4-phenylpiperaz inium (DMPP), a selective cholinergic nicotinic agonist, in dogs anest hetized with pentobarbital sodium. Plasma epinephrine and norepinephri ne concentrations were measured in adrenal venous and aortic blood by a high-performance liquid chromatography-electrochemical method. In th e vehicle control group, intravenous injection of DMPP (15 mu g/kg iv) produced a significant increase in adrenal venous catecholamine outpu t and aortic catecholamine concentration. These increasing responses w ere highly reproducible on the repetition of DMPP injection given 30 m in after the first injection. In dogs receiving nifedipine (100 mu g/k g iv), the net increase in adrenal venous epinephrine and norepinephri ne output in response to DMPP was attenuated by 42% (P < 0.05), while no significant changes were observed in the aortic catecholamine respo nse to DMPP. In dogs treated with pentolinium (1 mg/kg iv), both adren al epinephrine and norepinephrine responses to DMPP were inhibited by 67% (P < 0.05) and 84% (P < 0.05), respectively. Furthermore, pentolin ium inhibited aortic catecholamine response to DMPP by > 95% (P < 0.05 ). The present study suggests that DMPP-induced release of adrenal cat echolamines was mediated, at least in part, through mechanisms involvi ng dihydropyridine-sensitive L-type Ca2+ channels under in vivo condit ions. By contrast, however, the results also suggest that dihydropyrid ine-sensitive L-type Ca2+ channels were not implicated in the neurotra nsmission at the level of sympathetic ganglions.