SB 203220: a novel angiotensin II receptor antagonist and renoprotective agent.
SB 203220, [(E)-alpha-[[2-butyl-1-[(4-carboxy-1-naphthalenyl)-methyl]-1H- imidazol-5-yl]-methylene]-2-thiophene-propanic acid], is a novel nonpeptide angiotensin II receptor antagonist with significant oral activity. In the present study, we compared the cardiovascular and renal effects of SB 203220 and captopril in rats with chronic renal failure induced by 5/6 nephrectomy. Preliminary studies indicated that SB 203220 (600 ppm in the diet) and captopril (250 mg/l in drinking water) significantly attenuated the pressor activity of exogenous angiotensin II and angiotensin I, respectively. After 5/6 nephrectomy, significant hypertension was observed such that at 6 weeks, systolic blood pressure had reached 176 +/- 9 mm Hg. Both SB 203220 (128 +/- 18 mm Hg) and captopril (131 +/- 7 mm Hg) significantly attenuated the hypertension. Urinary protein excretion increased progressively after renal ablation (from 7 to 124 mg/day), and this was attenuated by both SB 203220 (32 +/- 7 mg/day) and captopril (42 +/- 6 mg/day). Assessment of serum creatinine and urea nitrogen indicated that SB 203220 but not captopril resulted in maintenance of renal function, close to that observed in control rats. Both SB 203220 and captopril attenuated the renal and left ventricular hypertrophy associated with 5/6 nephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
Brooks
D P
DP
Department of Renal Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania, USA.
Contino
L C
LC
Short
B G
BG
Gowan
C
C
Trizna
W
W
Edwards
R M
RM
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D004195:Disease Models, Animal; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D009281:Naphthalenes; D011945:Receptors, Angiotensin; D013876:Thiophenes; D000804:Angiotensin II; D002216:Captopril; C095799:SB 203220