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 release in response to nicotinic stimulation by 1,1-dimethyl-4-phenylpiperazinium (DMPP), a selective cholinergic nicotinic agonist, in dogs anesthetized with pentobarbital sodium. Plasma epinephrine and norepinephrine concentrations were measured in adrenal venous and aortic blood by a high-performance liquid chromatography-electrochemical method. In the vehicle control group, intravenous injection of DMPP (15 micrograms/kg iv) produced a significant increase in adrenal venous catecholamine output and aortic catecholamine concentration. These increasing responses were highly reproducible on the repetition of DMPP injection given 30 min after the first injection. In dogs receiving nifedipine (100 micrograms/kg iv), the net increase in adrenal venous epinephrine and norepinephrine output in response to DMPP was attenuated by 42% (P < 0.05), while no significant changes were observed in the aortic catecholamine response to DMPP. In dogs treated with pentolinium (1 mg/kg iv), both adrenal epinephrine and norepinephrine responses to DMPP were inhibited by 67% (P < 0.05) and 84% (P < 0.05), respectively. Furthermore, pentolinium inhibited aortic catecholamine response to DMPP by > 95% (P < 0.05). The present study suggests that DMPP-induced release of adrenal catecholamines was mediated, at least in part, through mechanisms involving dihydropyridine-sensitive L-type Ca2+ channels under in vivo conditions. By contrast, however, the results also suggest that dihydropyridine-sensitive L-type Ca2+ channels were not implicated in the neurotransmission at the level of sympathetic ganglions.
Gaspo
R
R
Groupe de Recherche sur le Système Nerveux Autonome, Faculté de Pharmacie, Université de Montréal, Quebec, Canada.
Yamaguchi
N
N
de Champlain
J
J
D000311:Adrenal Glands / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001011:Aorta; D001783:Blood Flow Velocity; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology*; D004285:Dogs; D004837:Epinephrine / Q000097:blood*; D007700:Kinetics; D008297:Male; D018733:Nicotinic Antagonists; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood*; D010425:Pentolinium Tartrate / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D014680:Veins
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide; D010425:Pentolinium Tartrate; D009543:Nifedipine; D009638:Norepinephrine; D004837:Epinephrine