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

• Published in: American journal of obstetrics and gynecology 2010-12, Vol.203 (6), p.596.e6-596.e12
• Main Authors: Xiao, Daliao, PhD, Longo, Lawrence D., MD, Zhang, Lubo, PhD
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Altitude; Animals; Arteries - drug effects; Arteries - physiology; Calcium Channels, L-Type - metabolism; Disease Models, Animal; Female; Hypoxia - physiopathology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Obstetrics and Gynecology; Phenylephrine - pharmacology; Pregnancy; Pregnancy, Animal; Random Allocation; Reference Values; Sheep; Sheep, Domestic; Uterus - blood supply; Vasoconstriction - drug effects; Vasoconstriction - physiology; Verapamil - pharmacology
• ISSN: 0002-9378; 1097-6868; 1097-6868
• DOI: 10.1016/j.ajog.2010.07.038

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 verapamil-induced 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 (-logEC50 ) 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 Ca2+ 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.