Systemic and renal effect of chronic omapatrilat in sodium-restricted, one-kidney, one-clip hypertensive rats.

摘要

OBJECTIVE: The systemic and renal effect of omapatrilat was evaluated and compared with that of enalapril (30 and 10 mg/kg per day) in sodium-depleted, one-kidney, one-clip hypertensive rats. Participation of kinins was assessed by concomitant infusion of Hoe140 (300 microg/kg per day). DESIGN: Four weeks after clipping and uninephrectomy, dietary sodium was withdrawn for 2 weeks and rats were treated during the last 6 days of the study. METHODS: Tail-cuff pressure and sodium excretion were determined in conscious rats. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined in anesthetized rats using clearance methods. The heart weight index was calculated. RESULTS: Omapatrilat was as effective as enalapril in reducing arterial pressure, and Hoe140 had no influence. Natriuresis increased to a similar extent with omapatrilat and enalapril. Hoe140 prevented the sodium loss only in enalapril-treated rats. Compared with untreated rats, GFR was reduced to a lesser extent by omapatrilatthan enalapril (694 +/- 93 and 364 +/- 40 versus 848 +/- 43 microl/min per g kidney weight). Hoe140 had no influence on GFR in omapatrilat-treated animals but attenuated the reduction of GFR in enalapril-treated rats (662 +/- 22 and 543 +/- 62 microl/min per g kidney weight). Since RPF was not significantly affected, reduction of the filtration fraction was more marked in enalapril- than omapatrilat-treated rats (60 and 28%, respectively). Heart weight index was lower in omapatrilat-treated rats than in untreated or enalapril-treated rats. Hoe140 failed to significantly obliterate the antihypertrophic effect of omapatrilat. CONCLUSION: These results suggest that accumulation of natriuretic peptides due to neutral endopeptidase inhibition participated in the antihypertrophic effect of omapatrilat and tended to counteract the deleterious effect of ACE inhibition on renal function.