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

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.