The role of cyclic nucleotides in the spontaneous contractility and responsiveness to nitric oxide of the rat uterus at midgestation and term.
OBJECTIVE
The aim of this investigation was to study the effects of pharmacologic manipulation of cyclic nucleotide levels on the uterine spontaneous contractile activity and responsiveness to nitric oxide in pregnant rats at midgestation and term.


METHODS
Uterine rings from pregnant rats at midgestation and term were placed in organ chambers for isometric tension recording. Concentration-response curves were obtained for phosphodiesterase and guanylate cyclase inhibitors, membrane-permeable cyclic nucleotide analogs, and forskolin. In addition, the effects of minimal inhibitory concentrations of these agents on the concentration-response relationships for diethylamine nitric oxide (a nitric oxide donor) were studied.


RESULTS
Nonselective phosphodiesterase inhibitors induced more inhibition of contractions of uterine rings from pregnant rats at term than at midgestation and zaprinast induced less. Inhibitors of guanylate cyclase and membrane-permeable analogs of cyclic guanosine monophosphate were equally effective in tissues from pregnant rats at midgestation and term. All agents attenuated the inhibitory effect of diethylamine nitric oxide at midgestation; however, dibutyryl cyclic adenosine monophosphate and papaverine increased the inhibitory effect of diethylamine nitric oxide in tissues from pregnant animals at term.


CONCLUSIONS
Cyclic nucleotides modulate both spontaneous and nitric oxide-induced changes in uterine contraction during pregnancy. Application of nonselective inhibitors of phosphodiesterase, as well as membrane-permeable analogs of cyclic adenosine monophosphate, may counteract refractoriness to nitric oxide at term.
Vedernikov
Y P
YP
Division of Reproductive Sciences and Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-1062, USA.
Syal
A S
AS
Okawa
T
T
Jain
V
V
Saade
G R
GR
Garfield
R E
RE
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology*; D010208:Papaverine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects*; D014599:Uterus / Q000187:drug effects*
D010726:Phosphodiesterase Inhibitors; D005576:Colforsin; D009569:Nitric Oxide; D010208:Papaverine; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine