Role of angiotensin II in dietary modulation of rat late distal tubule bicarbonate flux in vivo

We have reported that overnight fasting stimulates bicarbonate reabsorption (J(tCO2)) in rat distal tubules. The present in vivo microperfusion studies evaluated the hypothesis that endogenous angiotensin II (AII) mediates this response. Rat late distal (LD) tubules were perfused at 8 nl/min in vivo with a hypotonic solution containing 28 mM bicarbonate, In overnight-fasted rats, LDJ(tCO2) was significantly higher than in normally fed rats (50 +/- 4 vs 16 +/- 6 pmol/min . mm, P < 0.05). When overnight-fasted rats were salt-loaded, J,cor fell significantly (38 +/- 3 pmol/min . mm, P < 0.05). Conversely, in fed rats ingesting a zero-salt diet, J(tCO2) increased threefold (45 +/- 5 pmol/min . mm, P < 0.05), Enalaprilat infusion (0.25 mu/kg body wt, intravenously), in these zero-salt and overnight-fasted rats, reduced LDJ(tCO2) values to normal, Further, infusion of losartan (5 mg/kg body wt, intravenously), the specific AII AT(1) receptor blocker, reduced J(tCO2) in overnight-fasted rats by two-thirds (16 +/- 4 pmol/min mm, P < 0.05). Finally, we perfused 10(-11) M AII intraluminally with and without 10(-6) M losartan: Ail increased J(tCO2) to 45 +/- 6 pmol/min mm, equal to the zero-salt flux. This was completely abrogated by simultaneous losartan perfusion. Therefore, these results suggest that AII is an in vivo stimulator of late distal tubule bicarbonate reabsorption.