Renin-angiotensin inhibition reverses advanced cardiac remodeling in aging spontaneously hypertensive rats.

Abstract

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.

• Authors: Norihisa Ito, Mitsuru Ohishi, Koichi Yamamoto, Yuji Tatara, Atsushi Shiota, Norihiro Hayashi, Norio Komai, Yoshihiro Yanagitani, Hiromi Rakugi, Toshio Ogihara
• Journal: American journal of hypertension (Am J Hypertens) Vol. 20 Issue 7 Pg. 792-9 (Jul 2007) ISSN: 0895-7061 [Print] United States
• PMID: 17586415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Angiotensin-Converting Enzyme Inhibitors
• Biomarkers
• Transforming Growth Factor beta1
• Fibroblast Growth Factor 2
• NADPH Oxidases

Topics

• Aging (drug effects)
• Angiotensin II Type 1 Receptor Blockers (pharmacology, therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (pharmacology, therapeutic use)
• Animals
• Biomarkers (metabolism)
• Blood Pressure (drug effects)
• Cardiomegaly (drug therapy)
• Fibroblast Growth Factor 2 (metabolism)
• Fibrosis (drug therapy)
• Hypertension (drug therapy)
• Male
• Myocardium (metabolism)
• NADPH Oxidases (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Rats, Inbred SHR
• Renin-Angiotensin System (drug effects)
• Transforming Growth Factor beta1 (metabolism)