EFFECT OF ANGIOTENSIN-II RECEPTOR BLOCKADE ON PROXIMAL TUBULAR FLUID REABSORPTION

The effect of physiological concentrations of angiotensin II on proxim al tubular fluid reabsorption remains controversial. To investigate th e effect of blockade of intratubular AT(1) receptors on tubular reabso rption, losartan (10(-5) M) was administered by microperfusion into an early proximal convolution of halothane-anesthetized Sprague-Dawley r ats. Four parameters that depend on the rate of proximal fluid reabsor ption were measured: proximal intratubular pressure (P-prox), early an d late proximal flow rate, and early distal NaCl concentration. decrea sed by 0.5 +/- 0.1 mmHg, late proximal flow P-prox decreased by 0.5 +/ - 0.1 mmHg, late proximal flow rate decreased by 2.0 +/- 0.8 nl/min, a nd early distal NaCl concentration decreased by 4.3 +/- 0.8 mM (mean /- SE). No changes were observed after microperfusion with saline. Bec ause the tubuloglomerular feedback mechanism was operating in the clos ed-loop mode, the decreased NaCl load to the macula densa will be comp ensated by an increase in the single-nephron glomerular filtration rat e. In agreement with this, the early proximal flow rate, measured prox imal to the site of losartan administration, increased by 5.7 +/- 1.3 nl/min. The increase in the rate of proximal reabsorption between the early and late proximal convolutions was estimated to be 7.8 nl/min (s imilar to 36%). It is concluded that a decrease in local luminal angio tensin II levels and/or AT(1) receptor activity under free flow condit ions increases the rate of proximal tubular fluid reabsorption.