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 synthases (NOS), which are up-regulated during pregnancy. NO induces uterine quiescence, which is deemed necessary for the maintenance of pregnancy. Relaxin is known to promote uterine quiescence. Relaxin has also been shown to stimulate NO production in several targets. In this study we investigated the effects of relaxin on the NO biosynthetic pathway of the mouse uterus. Estrogenized mice were treated with relaxin (2 microg) for 18 h, and the uterine horns were used for determination of immunoreactive endothelial-type NOS and inducible NOS. Moreover, uterine strips from estrogenized mice were placed in an organ bath, and the effect of relaxin on K+-induced contracture was evaluated in the presence or absence of the NOS inhibitor nitro-L-arginine. Relaxin increases the expression of endothelial-type NOS in surface epithelium, glands, endometrial stromal cells, and myometrium, leaving inducible NOS expression unaffected. Moreover, relaxin inhibits myometrial contractility, 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 suggested that relaxin has a physiological role in the up-regulation of uterine NO biosynthesis during pregnancy.
Bani
D
D
Department of Anatomy, Histology and Forensic Medicine, University of Florence, Italy.
Baccari
M C
MC
Nistri
S
S
Calamai
F
F
Bigazzi
M
M
Sacchi
T B
TB
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D012065:Relaxin / Q000494:pharmacology / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*; D014599:Uterus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D009569:Nitric Oxide; D012065:Relaxin; D019001:Nitric Oxide Synthase; D011188:Potassium