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This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/H2337    most recent 01238.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Xiao, D. Articles by Zhang, L. Search for Related Content PubMed PubMed Citation Articles by Xiao, D. Articles by Zhang, L.

Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway

Department of Physiology and Pharmacology, Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California

Submitted 22 November 2005 ; accepted in final form 3 January 2006

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 intracellular Ca²⁺ concentration ([Ca²⁺]_i) as a 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. A 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 phorbol 12,13-dibutyrate induced a decrease in diameter in the absence of changes in [Ca²⁺]_i. Pressure-dependent myogenic responses were significantly decreased in PUA 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 MAPKK (MEK) inhibitor PD-098059 had no effect on NPUA but significantly enhanced myogenic responses of PUA. In the presence of PD-098059, there was no difference in pressure-induced myogenic responses between NPUA and PUA. The results suggest that pregnancy downregulates 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.

sheep; protein kinase C; extracellular signal-regulated kinase

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