The role of nitric oxide in the effects of ovarian steroids on spontaneous myometrial contractility in rats.
Forty ovariectomized rats were apportioned into one control and three experimental groups (n=10 each) to evaluate the role of nitric oxide in the effects of ovarian steroids on spontaneous myometrial contractility in rats. The control group (group Ov) received sesame oil once daily for 10 days, whereas rats in the experimental groups were treated with progesterone (2 mg/(rat day); group P), 17beta-estradiol (10 microg/(rat day); group E2), or progesterone and 17beta-estradiol together (group E2+P). The functionality of the arginine-nitric oxide synthase (NOS)-nitric oxide (NO) pathway in the uterine horns of sacrificed rats was evaluated in an isolated organ bath. L-Arginine, sodium nitroprusside (SNP) and 8-Br-cGMP decreased uterine contractile tension induced by electric field stimulation (EFS) in the Ov, P, and E2+P groups, but not in the E2 group. In addition, L-arginine was ineffective when applied together with a NOS inhibitor, L-nitro-N-arginine (L-NNA). The percentage of contractile inhibition was higher in the Ov and P groups compared to the E2+P group. Immunohistochemical evaluation revealed that expression of neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS) in smooth muscles and nerve cells did not differ among the groups. Expression of nNOS and eNOS was strongly evident in the E2 and E2+P groups at both surface and glandular epithelium of the endometrium. iNOS expression was increased in surface epithelium of the E2 and E2+P groups. However, iNOS expression was only increased in glandular epithelial cells of the E2+P group. In conclusion, the L-arginine-NOS-NO pathway inhibits myometrial contractions via cGMP-dependent and -independent mechanisms, and while progesterone maintains the nitric oxide effects, estrogen prevents them. These results suggest that NOS does not mediate the effects of estrogen.
Bulbul
A
A
Department of Physiology, Faculty of Veterinary Medicine, Afyon Kocatepe University, Afyon, Turkey. abulbul@aku.edu.tr
Yağci
A
A
Altunbaş
K
K
Sevimli
A
A
Celik
H A
HA
Karadeniz
A
A
Akdağ
E
E
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling / Q000662:veterinary; D007150:Immunohistochemistry / Q000662:veterinary; D009215:Myometrium / Q000187:drug effects* / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D010052:Ovariectomy / Q000662:veterinary; D011374:Progesterone / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects*
D020030:Nitric Oxide Donors; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D011374:Progesterone; D004958:Estradiol; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP