Temocaprilat or olmesartan significantly reversed age-related advanced cardiac hypertrophy and reduced cardiac oxidative stress compared to hydralazine or saline in aging hypertensive rats.
Does renin-angiotensin system inhibition reverse advanced cardiac remodeling in aging spontaneously hypertensive rats?
In aging spontaneously hypertensive rats, renin-angiotensin system inhibition reversed advanced cardiac hypertrophy and fibrosis, partly through suppression of oxidative stress.
BACKGROUND: Many experiments using young hypertensive animal models support the evidence that angiotensin-converting enzyme inhibitor or angiotensin receptor type 1 blocker attenuates the progression of cardiac hypertrophy. However, it is still unclear whether inhibiting the renin-angiotensin system can reverse age-related cardiac hypertrophy. To clarify the role of renin-angiotensin system inhibition in naturally advanced myocardial hypertrophy we treated spontaneously hypertensive, aging rats with an angiotensin-converting enzyme inhibitor or an angiotensin receptor type 1 blocker. METHODS: We used osmotic pumps to deliver the blood-pressure reducers temocaprilat, olmesartan, hydralazine, or saline for 4 weeks. RESULTS: Heart and body weights were significantly reduced in animals treated with temocaprilat or olmesartan compared with animals treated with hydralazine or saline. Histologic myocyte size and cardiac fibrosis were significantly attenuated by temocaprilat or olmesartan. Real-time polymerase chain reaction (PCR) revealed that temocaprilat or olmesartan suppressed expression of cardiac transforming growth factor-beta1 and fibroblast growth factor-2 mRNA, a marker of cardiac fibrosis. Cardiac and systemic oxidative stress assessed by 8-isoprostane levels was significantly reduced in animals treated with temocaprilat or olmesartan compared with hydralazine-treated or saline-treated rats. Renin-angiotensin system inhibition reduced cardiac expression of NAD(P)H oxidative components p22phox, p47phox, and gp91phox. CONCLUSIONS: Renin-angiotensin system inhibition can reverse age-related, advanced cardiac hypertrophy. The mechanism of reversal is partly due to suppression of cardiac oxidative stress.
Ito et al. (Fri,) conducted a other in Advanced cardiac hypertrophy and hypertension. Temocaprilat or olmesartan vs. Hydralazine or saline was evaluated on Heart and body weights, histologic myocyte size, and cardiac fibrosis. Temocaprilat or olmesartan significantly reversed age-related advanced cardiac hypertrophy and reduced cardiac oxidative stress compared to hydralazine or saline in aging hypertensive rats.