Selective Type 1 Angiotensin II Receptor Blockade Attenuates Oxidative Stress and Regulates Angiotensin II Receptors in the Canine Failing Heart

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2008 Jun 17

PMID 18553176

Citations 4

Authors

Gordon Moe

Andrea Konig

Peter Liu

Bodh I Jugdutt

Affiliations

Soon will be listed here.

Abstract

Background And Objective: Angiotensin II type 1 receptor (AT(1)R) blockade reduces vascular oxidative stress but whether myocardial oxidative stress represents a mechanism for the beneficial effect of AT(1)R blockade in heart failure is unclear. Furthermore, the impact of AT(1)R blockade on the expression of angiotensin II receptors in heart failure has not been well documented. Accordingly, we examined the impact of the AT(1)R blocker candesartan on hemodynamics, left ventricular (LV) remodeling (echocardiography), oxidative stress, and tissue expression of AT(1)Rs and angiotensin II type 2 receptors (AT(2)Rs) in a canine model of pacing-induced heart failure.

Methods And Results: Animals were randomized to rapid right ventricular-pacing (250 beats/min for 3 weeks) to severe heart failure and treated with candesartan (10 mg/kg daily, n = 8) or placebo (n = 8) from day 3 onwards, or no pacing (sham, n = 7). Candesartan significantly reduced mean pulmonary arterial and LV diastolic pressure, LV end-diastolic and end-systolic volume and ascites, increased cardiac output, dP/dt, and ejection fraction, while reversing the marked increase in aldehydes, a marker of oxidative stress, observed in the placebo group. Although candesartan did not alter LV AT(1)R protein expression compared to placebo or sham, it reversed the decrease in AT(2)R protein observed in the placebo group.

Conclusion: Our results indicate that in the pacing model of heart failure, chronic AT(1)R blockade attenuates hemodynamic deterioration and limits LV remodeling and dysfunction, in part by reversing oxidative stress and AT(2)R downregulation.

Citing Articles

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