Role of H2O2 in hypertension, renin-angiotensin system activation and renal medullary disfunction caused by angiotensin II

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Sousa, T (Author) FMUP; Oliveira, S (Author) Other; Afonso, J (Author) Other; Morato, M (Author) FFUP; Patinha, D (Author) Other; Fraga, S (Author) FMUP; Carvalho, F (Author) FFUP; Albino Teixeira, A (Author) FMUP

Journal

Title: British Journal of Pharmacology

Vol. 166

Pages: 2386-2401

ISSN: 0007-1188

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 31 Citations

Scopus - 35 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-002-70Q

DOI: 10.1111/j.1476-5381.2012.01957.x

Abstract (EN): BACKGROUND AND PURPOSE Activation of the intrarenal renin-angiotensin system (RAS) and increased renal medullary hydrogen peroxide (H2O2) contribute to hypertension. We examined whether H2O2 mediated hypertension and intrarenal RAS activation induced by angiotensin II (Ang II). EXPERIMENTAL APPROACH Ang II (200 ng.kg(-1).min(-1)) or saline were infused in Sprague Dawley rats from day 0 to day 14. Polyethylene glycol (PEG)-catalase (10 000 U.kg(-1).day(-1)) was given to Ang II-treated rats, from day 7 to day 14. Systolic blood pressure was measured throughout the study. H2O2, angiotensin AT(1) receptor and Nox4 expression and nuclear factor-kappa B (NF-kappa B) activation were evaluated in the kidney. Plasma and urinary H2O2 and angiotensinogen were also measured. KEY RESULTS Ang II increased H2O2, AT1 receptor and Nox4 expression and NF-kappa B activation in the renal medulla, but not in the cortex. Ang II raised plasma and urinary H2O2 levels, increased urinary angiotensinogen but reduced plasma angiotensinogen. PEG-catalase had a short-term antihypertensive effect and transiently suppressed urinary angiotensinogen. PEG-catalase decreased renal medullary expression of AT1 receptors and Nox4 in Ang II-infused rats. Renal medullary NF-kappa B activation was correlated with local H2O2 levels and urinary angiotensinogen excretion. Loss of antihypertensive efficacy was associated with an eightfold increase of plasma angiotensinogen. CONCLUSIONS AND IMPLICATIONS The renal medulla is a major target for Ang II-induced redox dysfunction. H2O2 appears to be the key mediator enhancing intrarenal RAS activation and decreasing systemic RAS activity. The specific control of renal medullary H2O2 levels may provide future grounds for the treatment of hypertension.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 16