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To compare the protective effect against cardiac and renal damage of a β-blocker, an angiotensin converting enzyme inhibitor and a calcium antagonist in severely hypertensive rats.Six-week-old male spontaneously hypertensive rats (n = 24) were given 100 mg/kg deoxycorticosterone and a 4% NaCl diet. They were then treated orally with vehicle, atenolol (70 mg/kg), enalapril (5 mg/kg) or nisoldipine (7 mg/kg) for 8 weeks.Control (vehicle-treated) rats developed marked hypertension after 8 weeks. The antihypertensive effect of the three drugs was similar, as were the reductions achieved in cardiac weight and aortic thickness. However, histological examination revealed that nisoldipine was significantly more effective than the other drugs in reducing renal arteriolar lesions and renal glomerular sclerosis. Only nisoldipine significantly improved plasma creatinine and the glomerular filtration rate.These findings suggest that calcium antagonists have a renoprotective effect in severely hypertensive rats, which may derive from the inhibition of arteriolar damage and glomerular sclerosis.