Effect of Furosemide on the Renal Guanylate Cyclase in Rat

Kim, Hak Sul; Chun, Choong Sung

Abstract

Furosemide acts primarily on the thick ascending limb of the loop of Henle and inhibits the chloride transport in this site, which is the main mechanism of diuretic action of furosemide However, the precise molecular mechanism of diuretic action of furosemide is still unknown. Recent studies have shown that cGMP might be involved in diuretic effect of furosemide. In this study, the effects of furosemide on the renal tissue level of cGMP in vivo and on the renal guanylate cyclase in vitro were investigated. Also, the influence of aspirin on these effects was examined. The results were as follows: 1. The renal tissue level of cGMP was increased after administration of furosemide, but decreased after administration of aspirin. A combined administration of furosemide and aspirin increased the renal tissue level of cGMP, but the degree of elevation was less than those of the furosemide group. 2. The renal guanylate cyclase activity was slightly increased by furosemide, but this increase was not significant. The renal guanylate cyclase activity was significantly increased by arachidonic acid. Furosemide potentiated the effect of arachidonic acid on renal guanylate cyclase activity, which was inhibited by aspirin. These results indicate that effect of furosemide on renal tissue level of cGMP may be indirect effect that furosemide activates guanylate cyclase by means of increasing prostaglandin synthesis.