Antisympathetic and hemodynamic property of a dual L/N-type Ca(2+) channel blocker cilnidipine in rats.
The in vivo antisympathetic property of a dual L/N-type Ca(2+) channel blocker cilnidipine compared with that of typical N-type Ca(2+) channel blockers has never been clarified. We investigated the effects of the drug on a sympathetic nerve-mediated vascular response and vasodilating action in rats in comparison with those of an N-type Ca(2+) channel blocker omega-conotoxin MVIIA. In pithed rats, omega-conotoxin MVIIA preferentially suppressed the sympathetic nerve stimulation-induced pressor response, whereas cilnidipine suppressed the pressor response induced by sympathetic nerve stimulation and angiotensin II. In anesthetized rats, cilnidipine or omega-conotoxin MVIIA decreased mean blood pressure, while heart rate was decreased by omega-conotoxin MVIIA, but slightly increased by cilnidipine. These results suggest that cilnidipine can affect sympathetic N-type Ca(2+) channels in addition to vascular L-type Ca(2+) channels in antihypertensive doses in the rat in vivo. The antisympathetic activity of cilnidipine is not excessive for an antihypertensive drug in comparison with that of omega-conotoxin MVIIA.
Takahara
Akira
A
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki 210-8681, Japan. akira_takahara@ajinomoto.com
Koganei
Hajime
H
Takeda
Tomoko
T
Iwata
Seinosuke
S
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013565:Sympatholytics / Q000494:pharmacology*; D020960:omega-Conotoxins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D013565:Sympatholytics; D020960:omega-Conotoxins; C078452:ziconotide; C065927:cilnidipine