Renal protective effects of angiotensin II receptor I antagonist CV-11974 in spontaneously hypertensive stroke-prone rats (SHR-sp).

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.