Regulator of G protein signaling 2 deficiency causes endothelial dysfunction and impaired endothelium-derived hyperpolarizing factor-mediated relaxation by dysregulating Gi/o signaling.

The Journal of Biological Chemistry
Patrick Osei-OwusuK J Blumer

Abstract

Regulator of G protein signaling 2 (RGS2) is a GTPase-activating protein for G(q/11)α and G(i/o)α subunits. RGS2 deficiency is linked to hypertension in mice and humans, although causative mechanisms are not understood. Because endothelial dysfunction and increased peripheral resistance are hallmarks of hypertension, determining whether RGS2 regulates microvascular reactivity may reveal mechanisms relevant to cardiovascular disease. Here we have determined the effects of systemic versus endothelium- or vascular smooth muscle-specific deletion of RGS2 on microvascular contraction and relaxation. Contraction and relaxation of mesenteric resistance arteries were analyzed in response to phenylephrine, sodium nitroprusside, or acetylcholine with or without inhibitors of nitric oxide (NO) synthase or K(+) channels that mediate endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation. The results showed that deleting RGS2 in vascular smooth muscle had minor effects. Systemic or endothelium-specific deletion of RGS2 strikingly inhibited acetylcholine-evoked relaxation. Endothelium-specific deletion of RGS2 had little effect on NO-dependent relaxation but markedly impaired EDHF-dependent relaxation. Acute, inducible deleti...Continue Reading

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Citations

Jan 4, 2013·PloS One·Shuzhen GuoEng H Lo
Dec 15, 2012·Journal of Cellular Biochemistry·Dae-Weon ParkSuk-Hwan Baek
Jul 21, 2015·PloS One·Patrick Osei-OwusuKendall J Blumer
Sep 1, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Sanchita BasuAaron Proweller
Jan 23, 2013·Hypertension·Anne Stine KvehaugenAnne Cathrine Staff
Dec 12, 2018·Current Opinion in Nephrology and Hypertension·Guorui Deng, Justin L Grobe
Apr 30, 2019·Journal of the American Heart Association·Jennifer N KochPatrick Osei-Owusu
Dec 15, 2015·Journal of Cardiovascular Pharmacology·Michel Félétou
Apr 28, 2018·Physiological Genomics·Katherine J PerschbacherJustin L Grobe
Jan 15, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Patrick Osei-OwusuRobert P Mecham

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