Intrarenal renin-angiotensin system contributes to tubular acidification adaptation following uninephrectomy

Background/Aims: Reduction in renal mass by uninephrectomy induces a functi onal compensation in the remnant kidney. The activity of the angiotensin-co nverting enzyme (ACE) as well as renin mRNA in the proximal convoluted tubu le (PCT) of uninephrectomized (UNx) rats increases. The aim of this work wa s to determine whether the increased activity of the local renin-angiotensi n system (RAS) participates in the adaptation of renal function after unine phrectomy. Method: We utilized normal two-kidney (2K) and 3-week UNx rats t o study the activity of the ACE in vesicles obtained from luminal membranes of proximal tubular cells and the acidification kinectics in PCTs using mi cropuncture techniques. Results: The converting enzyme activity was signifi cantly larger in UNx (5.87 +/- 0.69 nmol.min(-1).mg protein(-1)) than in 2K rats (2.43 +/- 0.13 nmol.min(-1).mg protein(-1); p < 0.05). The acidificat ion rate constant (kappa) in PCT of 2K rats was 0.18 +/- 0.02 s(-1) and in UNx rats 0.30 +/- 0.04 s(-1) (p < 0.001). In UNx rats, microperfusion with 10(-5) M ramipril or 10(-5) M losartan decreased kappa to 0.19 +/- 0.02 and 0.18 +/- 0.02 s(-1), respectively, but had no effect on 2K rats. Luminal s teady-state pH (pH(infinity)) was the same in 2K and UNx rats, and was not modified by addition of 10(-5) M ramipril or 10(-5) M losartan in both grou ps. The proximal H+ flux (J(H+),), calculated from pH(infinity), and kappa, was 1.12 nmol.cm(-2).s(-1) in 2K rats and, 1.77 nmol.cm(-2).s(-1) in UNx r ats (p < 0.001). In 2K rats, this value was not changed by 10(-5) M ramipri l or 10(-5) M losartan, but in UNx rats J(H+) decreased 25 and 30% with ram ipril or losartan, respectively (p < 0.001). Conclusions: These data sugges t that the increase in the local RAS activity could be an adaptive change t hat contributes to maintain the homeostasis of body fluids after uninephrec tomy. Copyright (C) 2000 S. Karger AG, Basel.