Increases in cyclic GMP levels may not mediate relaxant effects of sodium nitroprusside, verapamil and hydralazine in rat vas deferens

Abstract

IT has been suggested that increases in cyclic GMP levels may be responsible for the promotion of contractions in a variety of smooth muscles^1–6. This suggestion was based on observations that agents known to be capable of contracting smooth muscles produced marked increases in cyclic GMP levels in the respective muscles^1–8. However, recent reports have concluded that, although increases in cyclic GMP levels do occur during contractions in some types of smooth muscle, the increases in cyclic GMP levels are not responsible for the initiation or promotion of the contractions^9–12. Part of the evidence for this conclusion was the observation that marked increases in cyclic GMP levels occurred during relaxation of smooth muscles by drugs such as nitroglycerol^10,12. Schultz et al.¹³ have shown that other smooth muscle relaxants including sodium nitroprusside, hydralazine, and D-600 (a methoxy derivative of verapamil) are all capable of increasing cyclic GMP levels in isolated segments of rat vas deferens. These authors also noted that the 8-bromo derivative of cyclic GMP was itself capable of relaxing the rat vas deferens in certain conditions¹³. It was concluded that, not only was cyclic GMP not a mediator of smooth muscle contraction, but it might in fact be responsible for the smooth muscle relaxant effects of the above drugs. We describe here studies performed in rat vas deferens. Our results are not consistent with the hypothesis that increases in cyclic GMP levels are responsible for drug-induced smooth muscle relaxation.