Regulator of G protein signalling 2 ameliorates angiotensin II‐induced hypertension in mice

Resistant Hypertension, Elevated Aldosterone/Renin Ratio and Reduced RGS2: A Pathogenetic Link Deserving Further Investigations?

“…Although the precise mechanism for the up regulation of Rgs2 is not fully understood, recent findings have implicated a role for PLA2 (phospholipase A2) in this process. Together, these results suggest a reciprocal relationship between RGS2 and Ang II, which is supported by in vivo studies showing that the Rgs2-null animals are more sensitive to Ang II-induced hypertension than wild-type controls (Hercule et al, 2007).…”

“…Moreover, RGS2-null mice also have increased pressor responses to infusion of Ang II and -adrenergic receptor agonists compared with wild-type controls. This effect may be partly explained by increased myogenic vasoreactivity to Gprotein-mediated stimuli of the RGS2-null mice (Hercule et al, 2007). RGS2 has also been shown to be highly integrated within the NO mediated vasodilator pathway.…”

Identification of a cAMP-response Element in the Regulator of G-protein Signaling-2 (RGS2) Promoter as a Key Cis-regulatory Element for RGS2 Transcriptional Regulation by Angiotensin II in Cultured Vascular Smooth Muscles

“…8A). These observations raise the possibility that the three human RGS2 SNPs might negatively affect RGS2 mRNA expression, which might be expected to predispose to hypertension by analogy with effects of reduced RGS2 expression on blood pressure in genetically modified mice (3)(4)(5)(6)(7).…”

“…Increased expression of VSMC RGS2 mRNA by Ang II results in increased levels of RGS2 protein (16,18) and results in negative regulations of Ang II signaling (16,18). That these in vitro observations have physiologic significance is suggested by in vivo studies that indicate that Rgs2-null mice are more sensitive to Ang II-induced hypertension than their WT littermates (7). The molecular details of the signal transduction pathway that links the Ang II-AT1 receptor interaction to increased expression of RGS2 mRNA, however, are largely unknown.…”

“…RGS2 is expressed ubiquitously, and its major biological function is to serve as a GTPase-activating protein that preferentially attenuates heterotrimeric G protein G␣ q/11 GTPase activity (2). Several independent studies have demonstrated that Rgs2 knock-out mice have severe hypertension (3)(4)(5)(6)(7), suggesting that RGS2 plays a critical role in blood pressure homeostasis. Interestingly, heterozygous Rgs2 knockout mice are also hypertensive, and their blood pressures are virtually identical to homozygous Rgs2 knock-out mice (3), indicating that two functional Rgs2 alleles are required for normal blood pressure homeostasis.…”