Effect of cilnidipine, a novel dihydropyridine Ca2+ channel blocker, on adrenal catecholamine secretion in anesthetized dogs.
We investigated the effect of cilnidipine, a novel dihydropyridine Ca2+ channel blocker possessing blocking actions on N-type and L-type voltage-dependent Ca2+ channels (VDCCs), in comparison with the L-type VDCC blocker nifedipine, on adrenal catecholamine secretion in response to splanchnic nerve stimulation (SNS), acetylcholine (ACh), the nicotinic receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium (DMPP), and muscarine in anesthetized dogs. Ca2+ channel blockers and cholinergic agonists were infused and injected, respectively, into the adrenal gland through the phrenicoabdominal artery. Cilnidipine (0.3-3 microg/min) inhibited increases in both epinephrine (EPI) and norepinephrine (NE) output induced by SNS (2 Hz), ACh (1.5 microg), and DMPP (0.2 microg). However, cilnidipine inhibited increase in NE output induced by muscarine (1 microg) without affecting increase in EPI output. Nifedipine (0.3-3 microg/min) inhibited the ACh- and DMPP-induced increases in EPI and NE output without affecting the SNS- and muscarine-induced increases in EPI and NE output. From these results, it seems likely that the inhibition by cilnidipine of the SNS-induced EPI and NE secretion and of the muscarine-induced NE secretion is related to its blocking action on N-type VDCCs.
Nagayama
T
T
Department of Pharmacology, Pharmaceutical Institute, Tohoku University, Aobayama, Sendai, Japan.
Yoshida
M
M
Suzuki-Kusaba
M
M
Hisa
H
H
Kimura
T
T
Satoh
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002395:Catecholamines; D004095:Dihydropyridines; D009599:Nitroprusside; D004246:Dimethylphenylpiperazinium Iodide; D009116:Muscarine; C065927:cilnidipine; D009543:Nifedipine; D000109:Acetylcholine