RGS2 Is a Mediator of Nitric Oxide Action on Blood Pressure and Vasoconstrictor Signaling

Sun, Xiaoguang; Kaltenbronn, Kevin M.; Steinberg, Thomas H.; Blumer, Kendall J.

doi:10.1124/mol.104.007724

Cited by 94 publications

(59 citation statements)

References 43 publications

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“…18,20,27 Additionally, it has been suggested that RGS2 may act as a downstream effector of the NO-cGMP pathway, resulting in vascular relaxation by attenuating vasoconstrictor signaling, whereas suppression of this mechanism may facilitate development of hypertension. 25 In this context, Semplicini et al demonstrated an association between the rs4606 G allele and RGS2 expression in peripheral blood mononuclear cells in hypertensive patients, with the lowest values in GG homozygotes. 20 In a smaller number of subjects from the same study (cases and controls), RGS2 gene and protein expression were also reduced in fibroblasts from those carrying either the CG or GG genotype.…”

Section: Discussionmentioning

confidence: 98%

“…As with the majority of vasoconstrictors, Ang II signals via G proteincoupled receptors that are coupled to G q protein to increase intracellular calcium and subsequent responses, such as vasoconstriction. 3,25 Ang II may also exert some of its effects via G i protein signaling. 26 RGS2 acts as a GTPase activating protein, negatively regulating both G q/11 as well as G i/o proteins by enhancing the termination of the activated G protein state.…”

Section: Discussionmentioning

confidence: 99%

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Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

et al. 2013

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Preeclampsia is a pregnancy specific disorder and a risk factor for later cardiovascular disease. The cause and detailed pathophysiology remains unknown. G protein signaling is involved in a variety of physiological processes, including blood pressure regulation. We assessed whether distributions of 3 single nucleotide polymorphisms in genes coding for components of G protein signaling pathways that have been associated with hypertension differ between women with preeclampsia and normotensive pregnant women; the G protein β3 subunit gene ( GNB3 ) C825T polymorphism (rs5443), the angiotensin II type 1 receptor gene ( AGTR1 ) 3′UTR A1166C polymorphism (rs5186), and the regulator of G protein signaling 2 gene ( RGS2 ) 3′UTR C1114G polymorphism (rs4606). Two separate Norwegian study populations were used; a large population based study and a smaller, but clinically well-described pregnancy biobank. A descriptive study of 43 women with eclampsia was additionally included. In the population-based study, an increased odds of preeclampsia (odds ratio, 1.21; [95% confidence interval, 1.05–1.40]; P =0.009) and recurrent preeclampsia (odds ratio, 1.43; [95% confidence interval, 1.06–1.92];, P =0.017) was found in women carrying the rs4606 CG or GG genotype. In early-onset preeclamptic patients with decidual spiral artery biopsies available (n=24), the rs4606 CG or GG genotype was more frequent in those with acute atherosis (resembling early stage of atherosclerosis) compared with those without: odds ratio, 15.0; (95% confidence interval, 2.02–111.2); P =0.004. No association was found between preeclampsia and the rs5443 or the rs5186. The genotype distribution in eclamptic women was not different from preeclamptic women. In conclusion, RGS2 rs4606 may affect the risk and progression of preeclampsia.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

et al. 2013

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“…3 In RGS2 knockout mice, the two pathways are disrupted and a strong hypertensive phenotype is observed. [3][4][5] In addition, our group and Riddle's group have recently reported that polymorphisms of human RGS2 are associated with human hypertension in a Japanese general population and in American blacks. 6,7 Just recently, other Japanese group reported that the polymorphism of near RGS2 is also associated with the development of hypertension evaluated by home blood pressure measuring.…”

Section: Introductionmentioning

confidence: 93%

Association of intima-media thickening of carotid artery with genetic polymorphisms of the regulator of G-protein signaling 2 gene in patients with hypertension and in the general population

et al. 2011

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Regulator of G-protein signaling 2 (RGS2) is a key molecule in signal pathways of vasoactive peptides, such as angiotensin II and endothelin 1, and is believed to have an important role in the pathophysiology of atherosclerosis. We have previously reported that common polymorphisms of RGS2 are associated with hypertension in Japanese. In this study, we studied whether the three previously identified common polymorphisms of RGS2 (À638A4G, 1026T4A and 1891-1892delTC) could be implicated in carotid atherosclerosis in Japanese patients with hypertension (459 men and 382 woman) and in a Japanese general population (814 men and 956 woman). We assessed two criteria for carotid atherosclerosis: maximal intima-media thickness (M-IMT) and mean-IMT. When subjects with atherosclerotic lesions were defined as having mean-IMTZ1.0 mm, multivariate logistic regression analysis performed after adjusting for confounding factors showed a significant association of the three common polymorphisms, À638A4G (AA versus AG+GG: odds ratio (OR), 1.55; 95% confidence interval (CI), 1.105-2.185; P¼0.0113 only for the general population), 1026T4A (TT versus TA+AA: OR, 1.42; 95% CI, 1.027-1.972; P¼0.034 for hypertensive subjects and OR, 1.56; 95% CI, 1.129-2.151; P¼0.0071 for the general population), and 1891-1892delTC (II versus ID+DD: OR, 1.44; 95% CI, 1.043-2.008; P¼0.028 for hypertensive subjects, OR, 1.32; 95% CI 1.002-1.742; P¼0.048 for the total general population and OR 1.59; 95% CI 1.155-2.207; P¼0.0047 for the general population), with carotid atherosclerosis. When atherosclerosis was defined as M-IMT X1.0 mm, the values of M-IMT were also significantly different between the three genotypes in the three common polymorphisms. Taken together, these data suggest that genetic polymorphisms in RGS2 are associated with intima-media thickening of carotid artery in humans.

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“…RGS2 is one of the predominant RGS proteins in the cardiovascular system and has been shown to be crucial in the regulation of vascular tone and blood pressure. RGS2 deficiency in mice is associated with a hypertensive phenotype and an increased sensitivity, as well as prolonged responsiveness to vasoconstrictors (4)(5)(6). In addition, genetic polymorphisms of RGS2 are correlated with hypertension and intima-media thickening of carotid arteries in humans (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Adrenomedullin and adrenotensin increase the transcription of regulator of G-protein signaling 2 in vascular smooth muscle cells via the cAMP-dependent and PKC pathways

Mao¹,

Su²,

Lei³

et al. 2013

Molecular Medicine Reports

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Abstract. The regulator of G-protein signaling 2 (RGS2) has been shown to be crucial in the regulation of vascular tone and blood pressure. The vascular activities of adrenomedullin (ADM) and adrenotension (ADT), two natural peptides, are dependent upon the modulation of RGS2 expression. However, the effects and pathways involved in their modulation remain unknown. This study aimed to observe the changes of RGS2 expression in response to ADM and ADT in cultured vascular smooth muscle cells and to clarify the potential signaling pathways in vitro. In the present study, vascular smooth muscle cells (VSMCs) were cultured with ADM and ADT of various concentrations for different time periods, and the gene expression of RGS2 was analyzed by PCR. ADM significantly increased the gene expression at 0.5 h to ~35-fold of that at baseline, whereas ADT marginally increased the expression after 1-2 h. SQ22,536 and chelerythrine were used to block the protein kinase A (PKA) and PKC pathways activated by incubation with ADM. The gene expression of RGS2 was reduced by SQ22,536 only. Furthermore, when SQ22,536 and chelerythrine were added to the cells incubated with ADT, the gene expression was markedly reduced by both SQ22,536 and chelerythrine. In conclusion, ADM immediately showed a marked increase in the gene expression of RGS2 in cultured VSMCs via a cAMP-dependent pathway and ADT gradually showed a marginal increase in the gene expression via a cAMP-dependent pathway and a PKC pathway.

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RGS2 Is a Mediator of Nitric Oxide Action on Blood Pressure and Vasoconstrictor Signaling

Cited by 94 publications

References 43 publications

Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

Single Nucleotide Polymorphisms in G Protein Signaling Pathway Genes in Preeclampsia

Association of intima-media thickening of carotid artery with genetic polymorphisms of the regulator of G-protein signaling 2 gene in patients with hypertension and in the general population

Adrenomedullin and adrenotensin increase the transcription of regulator of G-protein signaling 2 in vascular smooth muscle cells via the cAMP-dependent and PKC pathways

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