CYCLIC GMP-INDEPENDENT EFFECTS OF NITRIC-OXIDE ON GUINEA-PIG UTERINE CONTRACTILITY

1 The role of nitric oxide (NO) in the regulation of uterine contracti lity has yet to be clearly defined. We evaluated the effect of NO (in the form of S-nitroso-L-cysteine, CysNO) upon uterine contractility an d guanosine 3',5'-cyclic monophosphate (cyclic GMP) accumulation in pr egnant and nonpregnant guinea-pig myometrium. 2 While CysNO had no eff ect upon spontaneous contractile activity in either pregnant or nonpre gnant uterine tissues, addition of CysNO resulted in an immediate and reversible relaxation of oxytocin- or acetylcholine (ACh)-evoked contr actions. 3 Relaxation of agonist-evoked contractions in response to Cy sNO was associated with significant elevations in intracellular cyclic GMP concentrations ([cyclic GMP](i)). 4 Elevations in [cyclic GMP](i) were not required for relaxation, as inhibition of guanylyl cyclase b y methylene blue prevented [cyclic GMP](i) accumulation while having n o effect upon the ability of CysNO to relax agonist-evoked contraction s. 5 Addition of the cyclic GMP-analogues, 8-Br-cyclic GMP and PET-cyc lic GMP, only at high concentrations, produced partial relaxation of a gonist-contracted tissues, suggesting the possibility that cyclic GMP may be sufficient but not necessary for myometrial relaxation. 6 Our s tudies not only provide evidence for a functional role for NO-modulati on of agonist-evoked contractions in the pregnant and nonpregnant guin ea-pig uterus, but also that these occur by a mechanism which is not d ependent upon guanylyl cyclase activity.