A subdepressor dose of candesartan reduced pressure overload-induced transient reactive oxygen species production, perivascular inflammation, and subsequent myocardial fibrosis in a rat model of aortic constriction.
Does candesartan reduce reactive oxygen species production, perivascular inflammation, and cardiac fibrosis in a rat model of pressure overload?
In a rat model of pressure overload, candesartan prevented myocardial fibrosis by reducing transient vascular reactive oxygen species production and early perivascular inflammation, independent of its blood pressure-lowering effect.
Oxidative stress is implicated in the pathogenesis of various cardiovascular diseases. We have shown that in Wistar rats with a suprarenal aortic constriction (AC), pressure overload-induced transient perivascular inflammation (monocyte chemoattractant protein-1 MCP-1 induction and macrophage accumulation) in the early phase is the determinant of reactive myocardial fibrosis and resultant diastolic dysfunction in the late phase. Thus, we investigated the role of reactive oxygen species production in cardiac remodeling in AC rats. Superoxide production and the footprint of lipid peroxidation were assessed using dihydroethidium staining and immunohistostaining against 4-hydroxy-2-nonenal (4-HNE), respectively. In sham rats, dihydroethidium and 4-HNE signals were scarcely found in the heart. At day 3, AC rats showed dihydroethidium signals mainly in the intramyocardial arterial wall, whereas modest 4-HNE staining was observed diffusely in the myocardium. These signals declined to lower levels by day 14 despite sustained hypertension. Chronic administration of a subdepressor dose of an angiotensin II type 1 receptor blocker candesartan reduced the pressure overload-induced dihydroethidium and 4-HNE signals at day 3. Moreover, candesartan decreased MCP-1 induction and macrophage infiltration at day 3 and prevented myocardial fibrosis at day 14, without affecting left ventricle and myocyte hypertrophy. In conclusion, acute pressure overload induced self-limited superoxide production mainly in the vascular wall. The reactive oxygen species production would contribute to the perivascular inflammation and subsequent myocardial fibrosis. Angiotensin II was suggested to have a pressure-independent effect on the reactive oxygen species production.
Kai et al. (Sun,) conducted a other in Pressure overload-induced cardiac remodeling. Candesartan vs. Vehicle was evaluated on Reactive oxygen species production, perivascular inflammation, and myocardial fibrosis. A subdepressor dose of candesartan reduced pressure overload-induced transient reactive oxygen species production, perivascular inflammation, and subsequent myocardial fibrosis in a rat model of aortic constriction.