Regulation of a1‐adrenoceptor‐mediated contractions of the uterine artery by PKC in pregnant sheep

Abstract

Little is known about the adaptation of contractile mechanisms of uterine arterial smooth muscle to pregnancy. We hypothesize that PKC plays an important role in the regulation of α1-adrenoceptor-mediated contractions of the uterine artery and their adaptation to pregnancy. Uterine arteries were isolated from pregnant ewes (~140 days gestation). α1-adrenoceptor-mediated contractions were measured with increasing concentrations of phenylephrine (PE) in half-log increments in the absence or presence of the PKC activator phorbol 12, 13-dibutyrate (PDBu) and/or PKC inhibitor GF-109203X (GF). PE produced dose-dependent contractions of uterine arteries. PDBu (0.3 and 1 μM) significantly decreased pD2 value and maximum contraction (Emax) induced by PE. GF itself (0.1, 0.3, 1 μM) markedly decreased pD2 value and Emax induced by PE in a dose dependent pattern. However, treatment with PDBu and 1 μM GF significantly increased pD2 and Emax as compared with PDBu treatment alone without GF. These results suggest that activation of PKC plays an inhibitory role in the regulation of α1-adrenoceptor-mediated contraction of the uterine arteries during late pregnancy, which is likely to be important in the adaptation of α1-adrenoceptor-mediated contractions to pregnancy. (Supported in part by NIH grants HL57787 and HD 31226)