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

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 NG-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 χ 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 NNO2). 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.