Increased expression of regulator of G protein signaling-2 (RGS-2) in Bartter's/Gitelman's syndrome.: A role in the control of vascular tone and implication for hypertension.

被引:75
作者
Calò, LA
Pagnin, E
Davis, PA
Sartori, M
Ceolotto, G
Pessina, AC
Semplicini, A
机构
[1] Univ Padua, Clin Med 4, Dept Clin & Expt Med, I-35100 Padua, Italy
[2] Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA
关键词
D O I
10.1210/jc.2004-0498
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Regulator of G protein signaling-2 (RGS-2) plays a key role in the G protein-coupled receptor (GPCR) angiotensin II (Ang II) signaling. NO and cGMP exert a vasodilating action also through activation and binding to RGS-2 of cGMP dependent protein kinase 1-alpha, which phosphorylates RSG-2 and dephosphorylates myosin light chain. In Bartter's/Gitelman's patients (BS/GS) Ang II related signaling and vasomotor tone are blunted. Experiments were planned to explore whether RGS-2 may play a role in BS/GS vascular hyporeactivity. NO metabolites and cGMP urinary excretion were also measured. Mononuclear cells (PBM) from six BS/GS patients and six healthy controls were used. PBM RGS-2 mRNA and RGS-2 protein were increased in BS/GS: 0.47 +/- 0.06 d.u. vs 0.32 +/- 0.04. (p<0.006) (RGS-2 mRNA), and 0.692+/-0.02 vs 0.363 +/- 0.06 (p < 0.0001) (RGS2 protein). Incubation of PBM with Ang II increased RGS-2 protein in controls (from 0.363 +/- 0.06 d.u. to 0.602 +/- 0.05; p < 0.0001) but not in BS/GS (from 0.692 +/- 0.02 to 0.711 +/- 0.02). NO2-/NO3- and cGMP urinary excretion were increased in BS/GS (0.46 +/- 0.13 vs 0.26 +/- 0.05 mumol/mumol of urinary creatinine, p<0.005, and 0.060 +/- 0.030 vs 0.020 +/- 0.01 p<0.009, respectively). These results demonstrate that RSG-2 is increased and maximally stimulated in BS/GS and human RGS-2 system reacts as predicted by knockout mice experiments. This is the first report of RGS-2 level in a human clinical condition characterized by altered vascular tone, underlines the importance of RGS-2 as a key regulator element for Ang II signaling and provides insight into the links between BS/GS genetic abnormalities and abnormal vascular tone regulation.
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收藏
页码:4153 / 4157
页数:5
相关论文
共 24 条
[1]  
BARTTER FC, 1981, HYPERTENSION, V3, P69
[2]  
Beadling C, 1999, J IMMUNOL, V162, P2677
[3]  
Calo L, 1998, BIOMED CHROMATOGR, V12, P97, DOI 10.1002/(SICI)1099-0801(199803/04)12:2<97::AID-BMC734>3.0.CO
[4]  
2-#
[5]  
Calò L, 1999, CLIN NEPHROL, V51, P12
[6]   Intracellular calcium signalling and vascular reactivity in Bartter's syndrome [J].
Calo, L ;
DAngelo, A ;
Cantaro, S ;
Rizzolo, M ;
Favaro, S ;
Antonello, A ;
Borsatti, A .
NEPHRON, 1996, 72 (04) :570-573
[7]   Reduced content of α subunit of Gq protein content in monocytes of Bartter and Gitelman syndromes:: Relationship with vascular hyporeactivity [J].
Calò, L ;
Davis, PA ;
Semplicini, A .
KIDNEY INTERNATIONAL, 2002, 61 (01) :353-354
[8]   Abnormalities of Gq-mediated cell signaling in Bartter and Gitelman syndromes [J].
Calò, L ;
Ceolotto, G ;
Milani, M ;
Pagnin, E ;
van den Heuvel, LP ;
Sartori, M ;
Davis, PA ;
Costa, R ;
Semplicini, A .
KIDNEY INTERNATIONAL, 2001, 60 (03) :882-889
[9]   Control of vascular tone in the syndromes of Bartter and Gitelman [J].
Calò, L ;
Davis, PA ;
Semplicini, A .
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES, 2000, 37 (06) :503-522
[10]   Oxidative stress-related factors in Bartter's and Gitelman's syndromes:: relevance for angiotensin II signalling [J].
Calò, LA ;
Pagnin, E ;
Davis, PA ;
Sartori, M ;
Semplicini, A .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2003, 18 (08) :1518-1525