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Enhanced endothelin receptor type B ‐mediated vasodilation and underlying [ Ca 2+ ] i in mesenteric microvessels of pregnant rats
Author(s) -
Mazzuca Marc Q,
Dang Yiping,
Khalil Raouf A
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12225
Subject(s) - vasoconstriction , vasodilation , endocrinology , medicine , phenylephrine , endothelin receptor , chemistry , endothelin 1 , endothelium , nitroarginine , endothelins , receptor , nitric oxide , nitric oxide synthase , blood pressure
Background and Purpose Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin‐1 ( ET ‐1) causes vasoconstriction via endothelin receptor type A ( ET A R ), but could activate ET B R in the endothelium and release vasodilator substances. However, the roles of ET B R in the regulation of vascular function during pregnancy and the vascular mediators involved are unclear. Experimental Approach Pressurized mesenteric microvessels from pregnant and virgin S prague– D awley rats were loaded with fura‐2/ AM for simultaneous measurement of diameter and [ Ca 2+ ] i . Key Results High KCl (51 mM) and phenylephrine (PHE) caused increases in vasoconstriction and [ Ca 2+ ] i that were similar in pregnant and virgin rats. ET ‐1 caused vasoconstriction that was less in pregnant than virgin rats, with small increases in [ Ca 2+ ] i . Pretreatment with the ET B R antagonist BQ ‐788 caused greater enhancement of ET ‐1‐induced vasoconstriction in pregnant rats. ACh caused endothelium‐dependent relaxation and decreased [ Ca 2+ ] i , and was more potent in pregnant than in virgin rats. ET ‐1 + ET A R antagonist BQ ‐123, and the ET B R agonists sarafotoxin 6c ( S 6c) and IRL ‐1620 caused greater vasodilation in pregnant than in virgin rats with no changes in [ Ca 2+ ] i , suggesting up‐regulated ET B R ‐mediated relaxation pathways. ACh ‐, S 6c‐ and IRL ‐1620‐induced relaxation was reduced by the NO synthase inhibitor N ω ‐nitro‐ l ‐arginine methyl ester, and abolished by tetraethylammonium or endothelium removal. W estern blots revealed greater amount of ET B R in intact microvessels of pregnant than virgin rats, but reduced levels in endothelium‐denuded microvessels, supporting a role of endothelial ET B R . Conclusions and Implications The enhanced ET B R ‐mediated microvascular relaxation may contribute to the decreased vasoconstriction and vascular resistance during pregnancy.