Ito Norihisa, Ohishi Mitsuru, Yamamoto Koichi, Tatara Yuji, Shiota Atsushi, Hayashi Norihiro, Komai Norio, Yanagitani Yoshihiro, Rakugi Hiromi, Ogihara Toshio
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Am J Hypertens. 2007 Jul;20(7):792-9. doi: 10.1016/j.amjhyper.2007.02.004.
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.
We used osmotic pumps to deliver the blood-pressure reducers temocaprilat, olmesartan, hydralazine, or saline for 4 weeks.
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.
Renin-angiotensin system inhibition can reverse age-related, advanced cardiac hypertrophy. The mechanism of reversal is partly due to suppression of cardiac oxidative stress.
许多使用年轻高血压动物模型的实验支持以下证据，即血管紧张素转换酶抑制剂或1型血管紧张素受体阻滞剂可减轻心脏肥大的进展。然而，抑制肾素-血管紧张素系统是否能逆转与年龄相关的心脏肥大仍不清楚。为了阐明抑制肾素-血管紧张素系统在自然进展性心肌肥大中的作用，我们用血管紧张素转换酶抑制剂或1型血管紧张素受体阻滞剂治疗自发性高血压老龄大鼠。
我们使用渗透泵持续4周给予降压药替莫卡普利、奥美沙坦、肼屈嗪或生理盐水。
与接受肼屈嗪或生理盐水治疗的动物相比，接受替莫卡普利或奥美沙坦治疗的动物心脏和体重显著降低。替莫卡普利或奥美沙坦可显著减轻组织学上的心肌细胞大小和心脏纤维化。实时聚合酶链反应（PCR）显示，替莫卡普利或奥美沙坦可抑制心脏转化生长因子-β1和成纤维细胞生长因子-2 mRNA的表达，这是心脏纤维化的一个标志物。与接受肼屈嗪治疗或生理盐水治疗的大鼠相比，接受替莫卡普利或奥美沙坦治疗的动物通过8-异前列腺素水平评估的心脏和全身氧化应激显著降低。抑制肾素-血管紧张素系统可降低心脏中NAD(P)H氧化成分p22phox、p47phox和gp91phox的表达。
抑制肾素-血管紧张素系统可逆转与年龄相关的晚期心脏肥大。逆转机制部分归因于对心脏氧化应激的抑制。
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