REGULATION OF CGMP-INDUCED RELAXATION AND CGMP-DEPENDENT PROTEIN-KINASE IN RAT MYOMETRIUM DURING PREGNANCY

Increases in guanosine 3',5'-cyclic monophosphate (cGMP induced by nit ric oxide (NO), nitrovasodilators, and atrial peptides correlate with relaxation of vascular smooth muscle. Relaxation of myometrial smooth muscle by increases in cGMP, however, has required unusually high conc entrations of the cyclic nucleotide. We tested the hypothesis that the sensitivity of myometrium to relaxation by cGMP is increased during p regnancy. Aortic smooth muscle was more sensitive to relaxation by cGM P than myometrial tissues, and, contrary to our hypothesis, myometrium from pregnant rats was least sensitive. Although levels of cGMP were elevated after treatment with the NO donor, S-nitroso-N-acetylpenicill amine, relaxation of myometrial tissues obtained from pregnant rats oc curred only at extraordinarily high concentrations. The levels of cGMP -dependent protein kinase (PKG) were significantly decreased in myomet rium from pregnant rats compared with myometrium from nonpregnant cycl ing animals or aortic smooth muscle. Administration of estradiol to ov ariectomized rats increased myometrial PKG expression, and progesteron e antagonized this response. We conclude that 1) myometrial tissues fr om pregnant rats are not sensitive to relaxation by cGMP and 2) this i nsensitisity to cGMP is accompanied by progesterone-mediated decreases in the level of PKG expression.