To assess the chronic antihypertensive and renal protective effects of losartan, a specific angiotensin II receptor antagonist, in the remnant kidney model of chronic renal failure, we administered losartan alone or in combination with enalapril, for 14 days to 5/6-nephrectomized spontaneously hypertensive rats (SHR). Eight-week-old SHR underwent 5/6 nephrectomy. One week after the operation, low-dose or high-dose losartan alone (1 or 10 mg/kg/day), or a combination of high-dose losartan and enalapril (6 mg/kg/day) was administered intraperitoneally via an osmotic minipump for 14 days. Low-dose losartan only slightly attenuated the increase in blood pressure. High dose losartan completely blocked the increase in blood pressure throughout the experiment. Simultaneous administration of enalapril did not modify the antihypertensive effects of losartan. Furthermore, high-dose losartan with enalapril, and low-dose or high-dose losartan alone significantly decreased urinary protein excretion to the same extent. These effects were sustained for the entire experiment and were not associated with any significant changes in body weight, fluid intake, urine volume, urinary electrolyte excretion, or serum creatinine. These results suggest that losartan might have a renal protective effect independent of its systemic antihypertensive action. In addition, they suggest that the antihypertensive and renoprotective effects of ACE inhibitors in this rat model are mainly due to inhibition of angiotensin II production rather than to stimulation of the kalliki ein-kinin system or the vasodilator prostaglandins. (Hypertens Res 1994; 17: 173-178).
- angiotensin II receptor antagonist
- angiotensin converting enzyme inhibitor
- spontaneously hypertensive rat
ASJC Scopus subject areas
- Internal Medicine
- Cardiology and Cardiovascular Medicine