Effect of cortisol on norepinephrine-mediated contractions in ovine uterine arteries

Abstract

Cortisol potentiated norepinephrine (NE)-mediated contractions in ovine uterine arteries (UA). We tested the hypothesis that cortisol regulated α1-adrenoceptor-mediated pharmacomechanical coupling differentially in nonpregnant UA (NUA) and pregnant UA (PUA). Cortisol (10 ng/ml for 24 h) significantly increased contractile coupling efficiency of α1-adrenoceptors in NUA, but increased α1-adrenoceptor density in PUA. Cortisol potentiated NE-induced inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] synthesis in both NUA and PUA, but increased coupling efficiency of α1-adrenoceptors to Ins(1,4,5)P3 synthesis only in NUA. Carbenoxolone alone did not affect NE-mediated Ins(1,4,5)P3 production, but significantly enhanced cortisol-mediated potentiation of NE-stimulated Ins(1,4,5)P3 synthesis in PUA. In addition, cortisol potentiated the NE-induced increase in Ca2+ concentration in PUA, but increased NE-mediated contraction for a given amount of Ca2+ concentration in NUA. Collectively, the results indicate that cortisol potentiates NE-mediated contractions differentially in NUA and PUA, i.e., by upregulating α1-adrenoceptor density leading to increased Ca2+ mobilization in PUA while increasing α1-adrenoceptor coupling efficiency and myofilament Ca2+ sensitivity in NUA. In addition, the results suggest that pregnancy increases type 2 11β-hydroxysteroid dehydrogenase activity in the UA.