Expression of iNOS mRNA and inhibitory effect of NO on uterine contractile activity in rats are determined by local rather than systemic factors of pregnancy.
Our purpose was to investigate whether the local or systemic factors of pregnancy are associated with inducible nitric oxide synthase (iNOS) mRNA expression and to determine the inhibitory effects of pharmacological agents that increase cGMP levels in rat myometrium. iNOS mRNA expression was determined in uterine tissues from nonpregnant rats and on day 17 of gestation in the pregnant and non-pregnant uterine horns by RT-PCR. In addition, uterine rings from the pregnant and non-pregnant uterine horns were placed in Krebs-Henseleit solution for isometric recordings of spontaneous contractions. Concentration-inhibition relationships to diethylamine/nitric oxide complex, 8-bromo-cGMP, and the selective phosphodiesterase V inhibitor were obtained. Compared to nonpregnant rats, expression of iNOS mRNA in myometrium increased during pregnancy, which was maximal on day 17, followed by a decrease on day 21 of gestation. Expression of iNOS mRNA at day 17 of gestation was greater in pregnant uterine horns than in nonpregnant ones. Maximal inhibition of phosphodiesterase V and increasing cGMP induced similar inhibition of spontaneous contractions in nonpregnant and pregnant uterine horns, while NO induced less inhibition in the former. The results suggest that the local pregnancy factor is needed for signal transduction from NO to soluble guanylate cyclase at a time when maximal expression of iNOS mRNA is evident.
Department of Obstetrics & Gynecology, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan. okawat@fmu.ac.jp
Toshiaki
T
Okawa
Kimisato
K
Asano
Hidenori
H
Takahashi
Satoshi
S
Hashimoto
Hiroshi
H
Anbe
Akira
A
Sato
Robert E
RE
Gafield
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006834:Hydrazines / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009589:Nitrogen Oxides; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D012995:Solubility; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*
D006834:Hydrazines; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D012333:RNA, Messenger; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006162:Guanylate Cyclase; D006152:Cyclic GMP