Antinephritic effect of SA-446, an angiotensin I converting enzyme inhibitor, on crescentic-type anti-GBM nephritis in rats.

Abstract

The present study was made to investigate the antinephritic effect of SA-446, an angiotensin I converting enzyme inhibitor, on the crescentic-type anti-glomerular basement membrane (anti-GBM) nephritis in rats. The nephritis was induced in male Sprague-Dawley rats weighing approx. 190 g by immunizing with rabbit r-globulin in Freund's complete adjuvant following i. v. injection of anti-GBM serum. SA-446 at doses of 5 and 25 mg/kg was given daily orally to rats from the day after injection of anti.GBM serum(the 1st day) to the 39 th day. SA-446 at doses of 5 and 25 mg/kg showed a tendency to reduce urinary protein excretion on the 12th and the 40th days and plasma choresterol level on the 40th day. In light microscopic observation of renal glomeruli on the 40th day, this drug at both doses remarkably prevented crescent formation, adhesion of capillary walls to Bowman's capsule and f ibrinoid degeneration. In addition, this drug at both doses also caused antihypertensive action from the 5 th day onwards. A highly significant positive correlation was recognized between blood pressure and crescent formation on the 40th day. It is concluded from these results that SA. 446 shows a beneficial action on the crescentic-type anti-GBM nephritis and may exert its action partly through lowing of blood pressure.