Jpn. J. Pharmacol. 87 (3), 208-213 (2001)

Effects of Calcium Antagonists on the Nitrergic Nerve Function in Canine Corpus Cavernosum

Tomio Okamura*, Hideyuki Fujioka and Kazuhide Ayajiki

Department of Pharmacology, Shiga University of Medical Science, Seta, Ohtsu 520-2192, Japan

*Corresponding author. FAX: +81-77-548-2183, E-mail: okamura@belle.shiga-med.ac.jp

Abstract: Effects of calcium antagonists on nitrergic nerve function were examined in the isolated canine corpus cavernosum. In the cavernous strips precontracted with phenylephrine, transmural electrical stimulation elicited frequency-dependent (2-5 Hz) relaxations that were abolished by N^G-nitro-L-arginine (10^-5 M), a nitric oxide (NO) synthase inhibitor; 1H[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ, 10^-6 M), a soluble guanylate cyclase inhibitor; and tetrodotoxin (3 ｴ 10^-7 M). The relaxations were not affected by treatment with nifedipine or nicardipine (10^-8-10^-6 M), L-type specific calcium channel inhibitors, but were significantly inhibited by amlodipine or cilnidipine, inhibitors of L- plus N-type calcium channels, in a concentration-related manner (10^-7-10^-6 M). All of the inhibitors used did not affect the relaxations induced by exogenous NO (acidifed NaNO₂). These findings suggest that N-type, but not L-type, calcium channels are responsible for increasing cytosolic free calcium, a prerequisite for the synthesis of NO, in the nitrergic dilator nerves innervating the corpus cavernosum.

Keywords: Corpus cavernosum, Nitrergic nerve, Transmural electrical stimulation, Calcium antagonist, Smooth muscle relaxation

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