Pre- or post-treatment with aminoguanidine attenuates a renal distal acidification defect induced by acute ureteral obstruction in rats

Abstract

Acute unilateral ureteral obstruction (UUO) impairs distal nephron acid secretion and stimulates expression of inducible nitric oxide synthase (iNOS) in post-obstructed kidney (POK). This study investigated the influence of pre- or post-treatment with aminoguanidine as a selective iNOS inhibitor on UUO-induced renal functional disturbances. To induce acute UUO, the left ureter in rats was ligated and released after 24 h. Then, a 3 h clearance period followed by bicarbonate loading and thereafter a 30 min clearance period were allocated. Aminoguanidine was administered either prior to the UUO induction or after release of the obstruction in the different rat groups, while untreated and sham groups received normal saline. During the first clearance period, fractional bicarbonate excretion and urinary pH increased markedly in the POK of the untreated group compared with the left kidney of sham group, and a large drop in the difference between urine and blood pCO2 (U-B pCO2) was observed after bicarbonate loading; all of these parameters were ameliorated in the pre-treated and post-treated groups. However, the UUO-induced decreases in creatinine clearance, sodium reabsorption, urine osmolality, and free-water reabsorption in the POK were attenuated only in the post-treated group. Therefore, the in vivo application of a selective iNOS inhibitor partially improved the acute UUO-induced distal nephron acidification defect, while post-treatment but not pre-treatment with aminoguanidine ameliorated decrements of glomerular filtration, sodium reabsorption, and urine-concentrating ability.