Relaxin up-regulates the nitric oxide biosynthetic pathway in the mouse uterus: Involvement in the inhibition of myometrial contractility

The uterus is a site of nitric oxide (NO) production and expresses NO synth ases (NOS), which are up-regulated during pregnancy. NO induces uterine qui escence, which is deemed necessary for the maintenance of pregnancy. Relaxi n is known to promote uterine quiescence. Relaxin has also been shown to st imulate NO production in several targets. In this study we investigated the effects of relaxin on the NO biosynthetic pathway of the mouse uterus. Est rogenized mice were treated with relaxin (2 mu g) for 18 h, and the uterine horns were used for determination of immunoreactive endothelial-type NOS a nd inducible NOS. Moreover, uterine strips from estrogenized mice were plac ed in an organ bath, and the effect of relaxin on K+-induced contracture wa s evaluated in the presence or absence of the NOS inhibitor nitro-L-arginin e. Relaxin increases the expression of endothelial-type NOS in surface epit helium, glands, endometrial stromal cells, and myometrium, leaving inducibl e NOS expression unaffected. Moreover, relaxin inhibits myometrial contract ility, and this effect is blunted by nitro-L-arginine, thus indicating that the L-arginine-NO pathway is involved in the relaxant action of relaxin on the myometrium. Because relaxin is elevated during pregnancy, it is sugges ted that relaxin has a physiological role in the up-regulation of uterine N O biosynthesis during pregnancy.