Xiang-Qun Hu, Rui Song, Chiranjib Dasgupta, Taiming Liu, Meijuan Zhang, Stephen Twum-Barimah, Arlin B. Blood, Lubo Zhang
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引用次数: 0
Abstract
The striking increase of uterine blood flow during pregnancy is essential for normal fetal development as well as for cardiovascular well-being of the mother. Yet, the underlying mechanisms of pregnancy-mediated vasodilatation of the uterine artery are not fully understood. In this study, we test the hypothesis that Rad, a monomeric G protein, is a novel regulatory mechanism in inhibiting CaV1.2 channel currents in uterine artery haemodynamic adaptation to pregnancy in a sheep model. We found that pregnancy significantly upregulates Rad expression and decreases CaV1.2 channel currents in uterine arterial smooth muscle cells. Rad knockdown ex vivo and in vivo increases CaV1.2 activity and channel window currents by reducing steady-state inactivation in uterine arteries of pregnant sheep, recapitulating the phenotype of uterine arteries in non-pregnant animals. Moreover, Rad knockdown in vivo in pregnant sheep enhances myogenic tone and phenylephrine-induced vasoconstriction of uterine arteries. Whereas knockdown of Rad has no effect on mesenteric arterial CaV1.2 channel activity and mean arterial blood pressure, it significantly increases uterine vascular resistance and decreases uterine artery blood flow. Our study reveals a novel cause-and-effect mechanism of Rad in pregnancy-induced suppression of CaV1.2 channel activity in uterine arteries to facilitate increased uterine blood flow, providing new insights into fundamental mechanisms of uterine haemodynamic adaptation to pregnancy.
Rad, a monomeric G protein, is upregulated in uterine arteries of pregnant sheep.
Rad knockdown ex vivo or in vivo increases CaV1.2 channel currents in uterine arteries from pregnant ewes.
In vivo knockdown of Rad elevates uterine vascular resistance and decreases uterine blood flow in pregnant sheep.
The study reveals a novel mechanism of Rad in pregnancy-induced suppression of CaV1.2 channel activity in uterine arterial haemodynamic adaptation to pregnancy.
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The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew.
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