The Role of K+Channels in Rabbit Cavernous Smooth Muscle Relaxation by Acetylcholine and Nitroprusside

Jung, Gyung Woo; Suh, Joon Duk; Yoon, Jong Byung

Abstract

It is well known that nitric oxide (NO) mediates smooth muscle relaxation via an increase in cyclic GMP (cGMP) 1evels. Acetylcholine (ACh) and nitroprusside (SNP) are known to mediate relaxation of cavernous smooth muscle via increasing the levels of NO. In recent years, the role of K+ channels in the hyperpolarization induced by nitrates and ACh in smooth muscle have been investigated. In this study, we attempted to characterize the role of K+ channel in rabbit cavernous smooth muscle relaxation by ACh and SNP under organ bath. Changes in isometric tension of corporal strips were monitored. The results were as follows; 1. The relaxant effects of ACh and SNP on contracted smooth muscle induced by 80 mM K' were less than those by phenylephrine. The ACh-induced relaxation was almost abolished in rabbit cavernous smooth muscle which endothelium was denuded, but the that of SNP was not affected by removal of endothelium. 2. Ng-nitro-L-arginine(L-NOARG) (3x0.00001M) and methylene blue (3x0.00001M) significantly inhibited the relaxant effect of ACh in cavernous smooth muscle, but that of SNP was not influenced by these drugs. The inhibition of L-NOARG on the relaxant effect of Ach was reversed by the addition of L-arginine(3x0.0001M). 3. Charybdotoxin (ChTx, 0.0000001M), significantly inhibited the relaxant effects of ACh,SNP and 8-Br-cGMP, but glibenclamide (0.00001M) and apamin (0.00001M) did not influence those of ACh and SNP 4. ACh (0.0001M} and SNP (0.0001M) increased the tissue content of cGMP The effect of ACh on the tissue content of cGMP was significantly affected by L-NOARG (3x0.00001M) and methylene blue (3x0.0000lM), but that of SNP was not influenced by these drugs. ChTx (0.000000lM) did not attenuate the accumulation of cGMP induced by ACh and SNP. Above results suggest that the relaxing effect of Ach and SNP on the isolated rabbit cavernous smooth muscle is associated with an increase in the tissue content of cGMP. Furthermore, ChTx sensitive-K+ channel-mediated hyperpolarization by increased cGMP may play a part in the relaxation of rabbit cavernous smooth muscle by ACh and SNP