Role of K_ATP and L-type Ca²⁺ channel activities in regulation of ovine uterine vascular contractility: Effect of pregnancy and chronic hypoxia

OBJECTIVE: Our objective was to determine whether the pregnancy and high altitude long-term hypoxia-mediated changes in uterine artery contractility were regulated by KATP and L-type Ca2+ channel activities. STUDY DESIGN: Uterine arteries were isolated from nonpregnant and near-term pregnant ewes that had been maintained at sea level (∼300 m) or exposed to high altitude (3801 m) for 110 days. Isometric tension was measured in a tissue bath. RESULTS: Pregnancy increased diazoxide, but not verapamil-induced relaxations. Long-term hypoxia attenuated diazoxide-induced relaxations in near-term pregnant uterine arteries, but enhanced verapamilinduced relaxations in nonpregnant uterine arteries. Diazoxide decreased the maximal response (Emax) of phenylephrine-induced contractions in near-term pregnant uterin arteries but not nonpregnant uterine arteries in normoxic sheep. In contrast, diazoxide had no effect on phenylephrine-induced Emax in near-term pregnant uterine arteries but decreased it in nonpregnant uterine arteries in long-term hypoxia animals. Verapamil decreased the Emax and pD2 (-logEC 50) of phenylephrine- induced contractions in both nonpregnant uterine arteries and near-term pregnant uterine arteries in normoxic and long-term hypoxia animals, except nonpregnant uterine arteries of normoxic animals in which verapamil showed no effect on the pD2. CONCLUSION: The results suggest that pregnancy selectively increases KATP, but not L-type Ca 2+ channel activity. Long-term hypoxia decreases the KATP channel activity, which may contribute to the enhanced uterine vascular myogenic tone observed in pregnant sheep at high altitude hypoxia. © 2010 Mosby, Inc. All rights reserved.