Prevention of nephrosclerosis and cardiac hypertrophy by captopril treatment of spontaneously hypertensive rats.

The relationship between hypertension and cardiovascular damage was assessed in three groups of spontaneously hypertensive rats (SHR): 1. stroke prone SHR (SHR-SP) treated orally with an angiotensin I converting enzyme inhibitor (captopril) (100-400 mg/L in the drinking water) from 6 to 35 weeks of age, 2. SHR-SP maintained on tap water until 30 weeks of age, 3. stroke resistant SHR (SHR-SR) maintained on tap water. The controls were Wister Kyoto rats (WKY) maintained on tap water. Captopril-treated SHR-SP showed blood pressure lower than that of untreated SHR-SP, similar to SHR-SR. The ratio of heart weight to body weight was 0.55% in SHR-SP, 0.39% in captopril-treated SHR-SP, 0.46% in SHR-SR, and 0.39% in WKY. The kidneys of SHR-SP showed glomerular sclerosis, glomerular fibrosis, tubular casts, interstitial cell infiltration and vascular wall thickening or hyperplasia of the small arteries and arterioles. The severe glomerular sclerosis was mostly distributed in the inner and middle portions of cortex. Immunohistological study showed IgG, C3 and fibrinogen in the glomeruli and arterioles in SHR-SP. In captopril-treated SHR-SP, similar to SHR-SR, only minor histological changes were seen and there was no deposition of IgG, C3 or fibrinogen. No changes were seen in WKY. Thus, it was concluded that nephrosclerosis and cardiac hypertrophy in SHR-SP are prevented by captopril. The role of the renin-angiotensin and kallikrein-kinin systems in organ pathogenesis in SHR-SP is discussed.