Chronic Kinin Blockade and Effect of Ramipril in Renal Adaptation to Sodium Restriction

Abstract

The contribution of endogenous kinins to impairment in renal adaptation to a 6-day period of dietary sodium withdrawal associated with treatment with ramipril (5 mg/kg per day) and losartan (30 mg/kg per day) was evaluated by use of concomitant chronic administration of the bradykinin B2-receptor antagonist Hoe 140 (150 or 300 micrograms/kg per day via subcutaneous osmotic pump). A similar level of higher cumulative sodium excretion was observed in ramipril- and losartan-treated rats compared with untreated animals, and the effect of ramipril was not affected by Hoe 140. Similarly, the fall in arterial pressure and the renal vasodilatation associated with ramipril and losartan were not modified by Hoe 140. Glomerular filtration rate (785 +/- 73 microL/min per g KW in untreated sodium-depleted rats) decreased to a larger extent in ramipril-treated rats compared with losartan-treated rats (371 +/- 78 and 550 +/- 55 microL/min per g KW, respectively). Hoe 140 markedly prevented the alteration in glomerular filtration rate associated with ramipril, thus resulting in a final glomerular filtration rate (543 +/- 41 microL/min per g KW) similar to that observed with losartan. These findings demonstrate that despite a lack of influence on arterial pressure and sodium balance, accumulation of kinins markedly contributes to deterioration of the glomerular filtration rate induced by ramipril in sodium-depleted rats.