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1 Center for Perinatal Biology, Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA
* To whom correspondence should be addressed. E-mail: lzhang{at}llu.edu.
The mechanisms of adaptation of uterine artery vascular tone to pregnancy are not fully understood. The present study tested the hypothesis that pregnancy decreases the PKC-mediated Ca2+ sensitivity of the contractile process and attenuates myogenic tone in resistance-sized uterine arteries. In pressurized uterine arteries from nonpregnant (NPUA) and near-term pregnant (PUA) sheep we measured, simultaneously in the same tissue, vascular diameter and vessel wall [Ca2+]i as function of intraluminal pressure. In both NPUA and PUA, membrane depolarization with KCl caused a rapid increase in [Ca2+]i and a decrease in diameter. Pressure increase from 20 to 100 mmHg resulted in a transient increase in diameter that was associated with an increase in [Ca2+]i, followed by myogenic contractions in the absence of further changes in [Ca2+]i. In addition, activation of PKC by PDBu induced a decrease in diameter in the absence of changes in [Ca2+]i. Pressure-dependent myogenic responses were significantly decreased in PUA as compared with NPUA. However, pressure-induced increases in [Ca2+]i were not significantly different between PUA and NPUA. The ratio of changes in diameter to changes in [Ca2+]i was significantly greater for pressure-induced contraction of NPUA than that of PUA. Inhibition of PKC by calphostin C significantly attenuated the pressure-induced vascular tone and eliminated the difference of myogenic responses between NPUA and PUA. In contrast, the MEK inhibitor, PD098059 had no effect on NPUA, but significantly enhanced myogenic responses of PUA. In the presence of PD098059, there was no difference in pressure-induced myogenic responses between NPUA and PUA. The results suggest that pregnancy down-regulates pressure-dependent myogenic tone of the uterine artery, which is partly due to increased MEK/ERK activity and decreased PKC signal pathway leading to a decrease in Ca2+ sensitivity of myogenic mechanism in the uterine artery during pregnancy.
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