Effects of clentiazem (TA-3090) and nifedipine on basal circulating catecholamine levels and on stimulation-evoked adrenal catecholamine secretion in anesthetized dogs.
The effects of TA-3090 (clentiazem) and nifedipine on basal sympathoadrenal activity and on the adrenal medullary response during splanchnic nerve stimulation were studied in dogs anesthetized with sodium pentobarbital. Plasma concentrations of epinephrine and norepinephrine were measured in aortic and adrenal venous blood before and after acute administration of the drugs, as well as during left splanchnic nerve stimulation before and after administration of drugs. Following intravenous injections, TA-3090 (30, 100, and 300 micrograms/kg) did not affect basal circulating catecholamine levels, whereas nifedipine (10, 30, and 100 micrograms/kg) markedly increased aortic epinephrine and norepinephrine concentrations in a dose-dependent manner in correlation with progressive decreases in mean arterial pressure. The changes in aortic epinephrine and norepinephrine concentrations were inversely related to those in mean arterial pressure (r = 0.603, p < 0.01; r = 0.536, p < 0.01; respectively). In response to direct splanchnic nerve stimulation (2 Hz, 2 ms, 1 min, 12 V), adrenal venous epinephrine and norepinephrine concentrations significantly increased, with a high degree of reproducibility. The catecholamine responses to splanchnic nerve stimulation were not affected by either TA-3090 or nifedipine at any dose tested. The present results suggest that the increases in circulating catecholamine levels following nifedipine administration are due to baroreflex activation secondary to the drug-induced hypotension. The study indicates that both TA-3090 and nifedipine did not significantly affect L-type Ca2+ channels related to catecholamine release in the adrenal medulla under the present experimental conditions.
Gaspo
R
R
Groupe de recherche sur le système nerveux autonome, Faculté de pharmacie, Université de Montréal, Québec, Canada.
Lamarche
L
L
Yamaguchi
N
N
de Champlain
J
J
Garceau
D
D
D000311:Adrenal Glands / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood* / Q000378:metabolism; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013153:Splanchnic Nerves / Q000187:drug effects
D002121:Calcium Channel Blockers; D002395:Catecholamines; C056595:clentiazem; D004110:Diltiazem; D009543:Nifedipine