Involvement of arginase in regulating myometrial contractions during gestation in the rat

Abstract

This study was designed to investigate the role of arginase in regulating myometrial contractions during gestation in the rat. Arginase activity in the myometrium was significantly decreased during the 7th-21st day of gestation, with the lowest value on the 14th day. However, the enzyme activity became significantly higher at term gestation (22nd day) than that in the non-pregnant myometrium. Arginase I protein was undetectable in the non-pregnant myometrium, at 7th and 14th day of gestation and after delivery. A slight positive signal for arginase I was detectable at 21st day of gestation. However, the protein was clearly up-regulated at term gestation (22nd day), although arginase II protein was down-regulated during gestation, with the lowest value on the 14th day. Gestational changes in arginase activity negatively correlated with those in cyclic GMP production, whereas the changes positively correlated with those in endogenous nitric oxide synthase (NOS) inhibitors and endothelin-1 (ET-1) contents. Myometrial arginase activity was inhibited by N(G)-hydroxy-L-arginine as an intermediate of NO production from L-arginine in a concentration-dependent manner. Both basal and stimulated guanylyl cyclase activities were enhanced at mid- and reduced at term gestation and after delivery, thereby partly increasing cyclic GMP production at mid- and partly decreasing the nucleotide production at term gestation and after delivery. These results suggest that the decreased arginase activity at mid-gestation possibly results from the down-regulation of arginase II protein. Whereas, the enhanced overall arginase activity at term gestation seems to be because of the induced functional arginase I in concert with the attenuated arginase II expression. The enhanced arginase activity at term gestation would be implicated in increasing myometrial contractions mediated by the increased ET-1. The increased peptide production at term gestation is possibly because of the reduced cyclic GMP production resulting from enhanced arginase activity, accumulated endogenous NOS inhibitors and attenuated guanylyl cyclase activity.