Oxidative stress-related factors in Bartter's and Gitelman's syndromes:: relevance for angiotensin II signalling

被引:50
作者
Calò, LA
Pagnin, E
Davis, PA
Sartori, M
Semplicini, A
机构
[1] Univ Padua, Clin Med 4, Dept Clin & Expt Med, I-35128 Padua, Italy
[2] Univ Calif Davis, Dept Internal Med Clin Nutr, Davis, CA USA
关键词
angiotensin II; atherosclerosis; signal transduction; vasoactive agents; vasoconstriction/dilation;
D O I
10.1093/ndt/gfg204
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Background. Bartter's and Gitelman's syndromes (BS/GS) have a blunted Gq protein-mediated cell signalling despite high circulating angiotensin II (Ang II) levels. This is associated with reduced Galphaq gene expression, intracellular inositol trisphosphate and Ca++ release, PKC activity and cell reactivity. Ang 11 is a powerful stimulator of vascular oxidases but BS/GS patients show reduced total volatile LDL oxidation products and reduced LDL susceptibility to oxidation suggesting low level of oxidative stress. Therefore, we evaluated oxidative stress-related proteins in plasma and monocytes of patients with BS/GS, at baseline and after Ang II stimulation. Methods. In two BS and seven GS patients, biochemically and genetically characterized, and in 10 age- and sex-matched control subjects, we measured total plasma antioxidant power (AOP), plasma peroxynitrite level and gene expression of the NADH/NADPH oxidase subunit p22(phox), TGFbeta and haeme oxygenase-1 (HO-1) in circulating monocytes in basal condition and after stimulation with Ang II. Furthermore, we investigated the (CT)-T-242 polymorphism of p22(phox), whose topography in a potential haeme-binding site suggests a role in the regulation of oxidative stress. Results. AOP was higher in BS/GS patients than in controls (3.27 +/- 0.95 mmol/l vs 1.05 +/- 0.16, P = 0.002), together with higher plasma renin activity and aldosterone level (9.88 +/- 4.64 vs 0.95 +/- 0.08 nmol Ang I/h/ml, P < 0.0001; and 0.73 +/- 0.13 vs 0.18 +/- 0.01 nmol/l, P < 0.0001, respectively). The plasma peroxynitrite level was undetectable both in patients and controls. mRNA expression of p22(phox) and TGFbeta was reduced in BS/GS patients compared to controls [0.35 +/- 0.08 vs 0.53 +/- 0.05 densitometric units (d.u.), P=0.005, and 0.82 +/- 0.07 vs 1.15 +/- 0.25 d.u., P=0.006, respectively]. HO-1 mRNA was increased in BS/GS patients in comparison to controls (0.88 +/- 0.07 vs 0.78 +/- 0.11 d.u., P = 0.037). After acute Ang II exposure, p22(phox), TGFbeta and HO-1 gene expression significantly increased only in controls (from 0.59 +/- 0.12 to 0.96 +/- 0.11, P < 0.001, from 0.97 +/- 0.1 to 1.27 +/- 0.22, P < 0.008, and from 0.62 +/- 0.1 to 0.82 +/- 0.09, P < 0.001, respectively). Finally, C242T polymorphism of p22(phox) was undetectable. Conclusions. The intracellular responses to Ang II mediated by reactive oxygen species are reduced in BS/GS patients. This may contribute to their vascular hyporeactivity.
引用
收藏
页码:1518 / 1525
页数:8
相关论文
共 23 条
[1]   Reactive oxygen species as mediators of signal transduction in cardiovascular disease [J].
Abe, J ;
Berk, BC .
TRENDS IN CARDIOVASCULAR MEDICINE, 1998, 8 (02) :59-64
[2]   The transforming growth factor beta system in kidney disease and repair: recent progress and future directions [J].
Basile, DP .
CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION, 1999, 8 (01) :21-30
[3]  
BELLOMO G, 1998, CLIN CHEM LAB MED, V36, pA41
[4]   A variant of p22phox, involved in generation of reactive oxygen species in the vessel wall, is associated with progression of coronary atherosclerosis [J].
Cahilly, C ;
Ballantyne, CM ;
Lim, DS ;
Gotto, A ;
Marian, AJ .
CIRCULATION RESEARCH, 2000, 86 (04) :391-395
[5]   Reduced susceptibility to oxidation of low-density lipoprotein in patients with overproduction of nitric oxide (Bartter's and Gitelman's syndrome) [J].
Calò, L ;
Sartore, G ;
Bassi, A ;
Basso, C ;
Bertocco, S ;
Marin, R ;
Zambon, S ;
Cantaro, S ;
D'Angelo, A ;
Davis, PA ;
Manzato, E ;
Crepaldi, G .
JOURNAL OF HYPERTENSION, 1998, 16 (07) :1001-1008
[6]   FULL PATTERN OF URINARY PROSTAGLANDINS IN BARTTER-SYNDROME [J].
CALO, L ;
CANTARO, S ;
PICCOLI, A ;
FAVARO, S ;
BONFANTE, L ;
BORSATTI, A .
NEPHRON, 1990, 56 (04) :451-452
[7]   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
[8]   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
[9]  
Davis PA, 1999, CIRCULATION, V99, P2709
[10]   Role of oxidative stress in cardiovascular diseases [J].
Dhalla, NS ;
Temsah, RM ;
Netticadan, T .
JOURNAL OF HYPERTENSION, 2000, 18 (06) :655-673