Nakamura T, Honma H, Ikeda Y, Kuroyanagi R, Takano H, Obata J, Sato T, Kimura H, Yoshida Y, Tamura K
Second Department of Internal Medicine, Yamanashi Medical College, Japan.
Blood Press Suppl. 1994;5:61-6.
This study was performed to examine the effects of blockade of the renin-angiotensin system on the development of hypertension and renal damage in stroke-prone spontaneously hypertensive rats (SHR-sp), using a non-peptide angiotensin II receptor antagonist, CV-11974. We examined changes in blood pressure, urinary protein excretion, creatinine clearance and renal morphology in CV-11974-treated SHR-sp rats and compared these variables with those in non-treated SHR-sp and Wistar Kyoto (WKY) rats, as well as in hydralazine-treated SHR-sp rats. CV-11974 lowered systolic blood pressure in a manner similarly to hydralazine (CV-11974 204 +/- 3, hydralazine 200 +/- 3, non-treated SHR-sp 284 +/- 9, WKY 155 +/- 5 mmHg), but reduced urinary protein excretion more than hydralazine (p < 0.01). There were no significant differences in creatinine clearance among experimental groups. The glomerulosclerosis index was greater in non-treated and hydralazine-treated SHR-sp rats than in CV-11974 treated SHR-sp and WKY rats (p < 0.01). Hydralazine-treated SHR-sp rats had a lower glomerulosclerosis index than the non-treated SHR-sp rats (p < 0.01). No significant differences were found in glomerulosclerosis index between CV-11974-treated SHR-sp and WKY rats. Tubular atrophy, tubular casts and interstitial fibrosis were observed in non-treated SHR-sp rats and, occasionally, in hydralazine-treated SHR-sp rats, but not in CV-11974-treated SHR-sp rats or WKY rats. These results indicate that the angiotensin II receptor antagonist was superior to hydralazine as far as renal protection was concerned. This suggests that renal damage in SHR-sp rats is associated not only with hypertension but also with activation of the renin-angiotensin system.
本研究旨在使用非肽类血管紧张素II受体拮抗剂CV - 11974，研究阻断肾素 - 血管紧张素系统对易中风自发性高血压大鼠（SHR - sp）高血压发展和肾损伤的影响。我们检测了CV - 11974处理的SHR - sp大鼠的血压、尿蛋白排泄、肌酐清除率和肾脏形态变化，并将这些变量与未处理的SHR - sp大鼠、Wistar Kyoto（WKY）大鼠以及肼屈嗪处理的SHR - sp大鼠的相应变量进行比较。CV - 11974降低收缩压的方式与肼屈嗪相似（CV - 11974 204±3，肼屈嗪200±3，未处理的SHR - sp 284±9，WKY 155±5 mmHg），但降低尿蛋白排泄的作用比肼屈嗪更强（p < 0.01）。各实验组之间的肌酐清除率无显著差异。未处理和肼屈嗪处理的SHR - sp大鼠的肾小球硬化指数高于CV - 11974处理的SHR - sp大鼠和WKY大鼠（p < 0.01）。肼屈嗪处理的SHR - sp大鼠的肾小球硬化指数低于未处理的SHR - sp大鼠（p < 0.01）。CV - 11974处理的SHR - sp大鼠和WKY大鼠之间的肾小球硬化指数无显著差异。在未处理的SHR - sp大鼠中观察到肾小管萎缩、肾小管管型和间质纤维化，偶尔在肼屈嗪处理的SHR - sp大鼠中也有观察到，但在CV - 11974处理的SHR - sp大鼠或WKY大鼠中未观察到。这些结果表明，就肾脏保护而言，血管紧张素II受体拮抗剂优于肼屈嗪。这表明SHR - sp大鼠的肾损伤不仅与高血压有关，还与肾素 - 血管紧张素系统的激活有关。
