SB-203220 - A NOVEL ANGIOTENSIN-II RECEPTOR ANTAGONIST AND RENOPROTECTIVE AGENT

SE 203220, l]-1H-imidazol-5-yl]-methylene]-2-thiophene-acid], is a nov el nonpeptide angiotensin II receptor antagonist with significant oral activity. In the present study, we compared the cardiovascular and re nal effects of SE 203220 and captopril in rats with chronic renal fail ure induced by 5/6 nephrectomy. Preliminary studies indicated that SE 203220 (600 ppm in the diet) and captopril (250 mg/l in drinking water ) significantly attenuated the presser activity of exogenous angiotens in II and angiotensin I, respectively. After 5/6 nephrectomy, signific ant hypertension was observed such that at 6 weeks, systolic blood pre ssure had reached 176 +/- 9 mm Hg. Both SE 203220 (128 +/- 18 mm Hg) a nd captopril (131 +/- 7 mm Hg) significantly attenuated the hypertensi on. Urinary protein excretion in creased progressively after renal abl ation (from 7 to 124 mg/day), and this was attenuated by both SE 20322 0 (32 +/- 7 mg/day) and captopril (42 +/- 6 mg/day). Assessment of ser um creatinine and urea nitrogen indicated that SE 203220 but not capto pril resulted in maintenance of renal function, close to that observed in control rats. Both SE 203220 and captopril attenuated the renal an d left ventricular hypertrophy associated with 5/6 nephrectomy. Reduce d glomerulosclerosis, glomerular hypertrophy and tubular interstitial scores were observed in kidneys of rats treated with SE 203220 and cap topril compared with ablation control rats. The present study indicate s that SE 203220 is as effective as captopril in attenuating the progr ession of chronic renal failure in rats.