K. Kohara et al., ANGIOTENSIN BLOCKADE AND THE PROGRESSION OF RENAL DAMAGE IN THE SPONTANEOUSLY HYPERTENSIVE RAT, Hypertension, 21(6), 1993, pp. 975-979
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.