Comparative relaxant effects of YC-1 and DETA/NO on spontaneous contractions and the levels of cGMP of isolated pregnant rat myometrium.
This study was designed to compare the effects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole), a nitric oxide (NO)-independent soluble guanylate cyclase activator, and diethylenetriamine-NONOate (DETA/NO), a NO donor, on spontaneous contractions and the levels of cyclic GMP (cGMP) of myometrial strips isolated from timed-pregnant rats. Myometrial strips were obtained from timed-pregnant Wistar albino rats (n=10) and were mounted in organ baths and tested for changes in isometric tension in response to YC-1 and DETA/NO. We also evaluated the effect of YC-1 and DETA/NO on the levels of cGMP in myometrial strips obtained from timed-pregnant rat uterine horns (n=20). YC-1 (10(-9)-3x10(-5) M) and DETA/NO (10(-7)-10(-4) M) concentration-dependently decreased the amplitude and frequency of spontaneous contractions of myometrial strips isolated from term-pregnant rats. The inhibitions of the amplitude and frequency of spontaneous contractions by YC-1 and DETA/NO were antagonized with methylene-blue (10(-5) M). Antagonistic effect of methylene-blue (10(-5) M) was more on DETA/NO responses than that of YC-1 (P<0.05). In addition, YC-1-stimulated myometrial strips showed more elevation in myometrial cGMP than that of DETA/NO (P<0.05). We demonstrated that YC-1 and DETA/NO induce relaxations in the amplitude and frequency of spontaneous contractions of myometrial strips with different potencies. We also found that YC-1 and DETA/NO-induced relaxations are associated with significant increases in cGMP. These results might suggest that the relaxant effects of YC-1 and DETA/NO on the rat myometrium could be due to the stimulation of the soluble guanylate cyclase and cGMP may play a role for the maintenance of uterine quiescence during pregnancy.
Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, 58140, Sivas, Turkey.
Nihal
N
Demirkoprulu
Meral
M
Cetin
Ihsan
I
Bagcivan
Tijen
T
Kaya
Ahmet Serdar
AS
Soydan
Baris
B
Karadas
Ali
A
Cetin
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014226:Triazenes / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D007191:Indazoles; D020030:Nitric Oxide Donors; D014226:Triazenes; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D006152:Cyclic GMP; D008751:Methylene Blue