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Hypotension in RGS5‐deficient mice
Author(s) -
Cho Hyeseon,
Park Chung,
Hwang IlYoung,
Han SangBae,
kehrl John H.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.907.9
Subject(s) - vasodilation , vascular smooth muscle , endocrinology , medicine , g protein , nitric oxide , sodium nitroprusside , g protein coupled receptor , pharmacology , chemistry , microbiology and biotechnology , biology , receptor , smooth muscle
RGS5, a potent GTPase activating protein for Gi and Gq, and a member of the RGS family proteins is highly expressed in pericytes and present in vascular smooth muscle cells. In this study, we demonstrate that targeted deletion of Rgs5 in mice induces low blood pressure that is greater in female than male mice without concomitant cardiac dysfunction. The aorta of RGS5‐deficeint mice is dilated compared to that of littermate control mice without altered vessel thickness. Consistently, phosphorylation of vasodilator‐stimulated protein and ERK are enhanced in response to sodium nitroprusside or sphingosine‐1‐phosphate in aortic vascular smooth muscle cells prepared from Rgs5 −/− mice. In addition, these mice are lean compared to littermate controls. Our study along with previous studies demonstrating that the protein stability of RGS5 is likely under the control of nitric oxide via the N‐end rule pathway suggest that RGS5 may balance vascular tone by attenuating vasodilatory signaling in vivo in opposition to RGS2, another RGS family member known to inhibit GPCR‐mediated vasoconstrictor signaling. Blocking the functionor expression of RGS5 may provide an alternative approach to treat hypertension.