ANGIOTENSIN BLOCKADE AND THE PROGRESSION OF RENAL DAMAGE IN THE SPONTANEOUSLY HYPERTENSIVE RAT

The pathophysiological role of angiotensin II in the development of re nal sclerosis was investigated in 5/6-nephrectomized, 12-week-old male spontaneously hypertensive rats. After 1 week of a control period, ne phrectomized rats received one of the following treatments for 4 weeks : the selective nonpeptide angiotensin II type 1 receptor antagonist T CV-116 (1 mg/kg per day), the angiotensin converting enzyme inhibitor delapril (30 mg/kg per day), hydralazine (15 mg/kg per day), or vehicl e. Urinary protein and albumin excretions and systolic blood pressure were determined every week. Rats with reduced renal mass treated with vehicle had a poor survival rate (30%). Although TCV-116, delapril, an d hydralazine treatment significantly improved the survival rate for 4 weeks, hydralazine failed to improve proteinuria and albuminuria as w ell as the decline in renal function compared with delapril or TCV-116 . Histological examination revealed that both TCV-116 and delapril pro tected glomeruli from sclerosis, whereas hydralazine did not improve h istological findings (5%, 7%, and 30% of glomeruli were affected, resp ectively). These results indicate that angiotensin II plays a dominant role through its type 1 receptor in the pathogenesis of renal deterio ration by hypertension.