Regulation of Smooth Muscle Activity in the Rat: Effects of Castration and Iberiotoxin

Abstract

The mechanism by which smooth muscle contracts and relaxes has been intensely studied; however, many aspects have yet to be explained. The regulation of intracellular calcium concentrations within the smooth muscle cells essentially determines the flaccid/erect state of the penis. One factor identified to influence both contractile and relaxation mechanisms are the presence/absence of testosterone. The present investigated (1) whether castration (androgen-depleted cavernosal tissue) would have a differential effect on contraction and relaxation (Phase 1 or Phase 2) and (2) investigated whether inhibition of BK channels would effect the individual phases (Phase 1 and 2) of relaxation and test whether the presence/absence of androgens influenced BK channels. Corpus cavernosal tissue was removed from laboratory rats and tested in vitro on isometric force transducers. Tissues were contracted with norepinephrine and relaxed by sodium nitroprusside. BK channels were inhibited by the highly-selective antagonist iberiotoxin. Data was collected for contractile tension, percent total relaxation, percent of Phase 1, rate of Phase 1 relaxation, and percent of Phase 2 relaxation. Castration was found to significantly increase cavernosal tissue response to the norepinephrine; castration also decreased the response of the cavernosal tissue to the sodium nitroprusside. Further analysis of relaxation found the initial phase of relaxation was significantly reduced and the second phase was significantly greater, presumably due to castration. Inhibition of BK channels significantly slowed the rate of relaxation in Phase 1, while it tended to decrease percent total and Phase 1 relaxation. At least part of the supportive role of testosterone in normal erectile physiology is accomplished through the Phase 1 mechanism of relaxation and potentially the BK channels.