Angiotensin blockade and the progression of renal damage in the spontaneously hypertensive rat.
The pathophysiological role of angiotensin II in the development of renal sclerosis was investigated in 5/6-nephrectomized, 12-week-old male spontaneously hypertensive rats. After 1 week of a control period, nephrectomized rats received one of the following treatments for 4 weeks: the selective nonpeptide angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme inhibitor delapril (30 mg/kg per day), hydralazine (15 mg/kg per day), or vehicle. 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, and hydralazine treatment significantly improved the survival rate for 4 weeks, hydralazine failed to improve proteinuria and albuminuria as well as the decline in renal function compared with delapril or TCV-116. Histological examination revealed that both TCV-116 and delapril protected glomeruli from sclerosis, whereas hydralazine did not improve histological findings (5%, 7%, and 30% of glomeruli were affected, respectively). These results indicate that angiotensin II plays a dominant role through its type 1 receptor in the pathogenesis of renal deterioration by hypertension.
Kohara
K
K
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Mikami
H
H
Okuda
N
N
Higaki
J
J
Ogihara
T
T
D000419:Albuminuria / Q000652:urine; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007189:Indans / Q000494:pharmacology; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D016019:Survival Analysis; D013777:Tetrazoles
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007189:Indans; D013777:Tetrazoles; D000804:Angiotensin II; D006830:Hydralazine; D000803:Angiotensin I; C077793:candesartan cilexetil; C047759:delapril