PMID- 12897089
OWN - NLM
STAT- MEDLINE
DCOM- 20031117
LR  - 20190513
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 18
IP  - 8
DP  - 2003 Aug
TI  - Oxidative stress-related factors in Bartter's and Gitelman's syndromes: relevance 
      for angiotensin II signalling.
PG  - 1518-25
AB  - 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 
      II 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 
      C(242)T 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, C(242)T 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.
FAU - Calo, Lorenzo A
AU  - Calo LA
AD  - Department of Clinical and Experimental Medicine, Clinica Medica 4, University of 
      Padova, Italy. renzcalo@unipd.it
FAU - Pagnin, Elisa
AU  - Pagnin E
FAU - Davis, Paul A
AU  - Davis PA
FAU - Sartori, Michelangelo
AU  - Sartori M
FAU - Semplicini, Andrea
AU  - Semplicini A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transforming Growth Factor beta)
RN  - 11128-99-7 (Angiotensin II)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (CYBA protein, human)
RN  - EC 1.6.99.1 (NADPH Dehydrogenase)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.56 (Inositol Polyphosphate 5-Phosphatases)
SB  - IM
MH  - Adult
MH  - Angiotensin II/*metabolism
MH  - Bartter Syndrome/*physiopathology
MH  - Female
MH  - Humans
MH  - Inositol Polyphosphate 5-Phosphatases
MH  - Male
MH  - *Membrane Transport Proteins
MH  - Middle Aged
MH  - NADPH Dehydrogenase/metabolism
MH  - NADPH Oxidases
MH  - Oxidative Stress/*physiology
MH  - Peroxynitrous Acid/blood
MH  - Phosphoproteins/metabolism
MH  - Phosphoric Monoester Hydrolases/metabolism
MH  - Polymerase Chain Reaction
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/physiology
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2003/08/05 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/08/05 05:00
PHST- 2003/08/05 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/08/05 05:00 [entrez]
AID - 10.1093/ndt/gfg204 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2003 Aug;18(8):1518-25. doi: 10.1093/ndt/gfg204.