Word R A, Cornwell T L
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9032, USA.
Am J Physiol. 1998 Mar;274(3):C748-56. doi: 10.1152/ajpcell.1998.274.3.C748.
Increases in guanosine 3',5'-cyclic monophosphate (cGMP) induced by nitric 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 concentrations of the cyclic nucleotide. We tested the hypothesis that the sensitivity of myometrium to relaxation by cGMP is increased during pregnancy. Aortic smooth muscle was more sensitive to relaxation by cGMP 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-acetylpenicillamine, relaxation of myometrial tissues obtained from pregnant rats occurred only at extraordinarily high concentrations. The levels of cGMP-dependent protein kinase (PKG) were significantly decreased in myometrium from pregnant rats compared with myometrium from nonpregnant cycling animals or aortic smooth muscle. Administration of estradiol to ovariectomized rats increased myometrial PKG expression, and progesterone antagonized this response. We conclude that 1) myometrial tissues from pregnant rats are not sensitive to relaxation by cGMP and 2) this insensitivity to cGMP is accompanied by progesterone-mediated decreases in the level of PKG expression.
一氧化氮（NO）、硝基血管扩张剂和心房肽诱导的3',5'-环磷酸鸟苷（cGMP）增加与血管平滑肌舒张相关。然而，cGMP增加引起的子宫肌层平滑肌舒张需要异常高浓度的环核苷酸。我们检验了以下假设：孕期子宫肌层对cGMP舒张作用的敏感性增加。主动脉平滑肌对cGMP舒张作用的敏感性高于子宫肌层组织，与我们的假设相反，孕鼠的子宫肌层最不敏感。尽管用NO供体S-亚硝基-N-乙酰青霉胺处理后cGMP水平升高，但仅在极高浓度下孕鼠子宫肌层组织才会出现舒张。与未孕周期动物的子宫肌层或主动脉平滑肌相比，孕鼠子宫肌层中cGMP依赖性蛋白激酶（PKG）水平显著降低。给去卵巢大鼠注射雌二醇可增加子宫肌层PKG表达，而孕酮可拮抗这一反应。我们得出结论：1）孕鼠的子宫肌层组织对cGMP舒张作用不敏感；2）对cGMP的这种不敏感性伴随着孕酮介导的PKG表达水平降低。
