Effect of angiotensin II receptor blockade on proximal tubular fluid reabsorption.
The effect of physiological concentrations of angiotensin II on proximal tubular fluid reabsorption remains controversial. To investigate the effect of blockade of intratubular AT1 receptors on tubular reabsorption, losartan (10(-5) M) was administered by microperfusion into an early proximal convolution of halothane-anesthetized Sprague-Dawley rats. Four parameters that depend on the rate of proximal fluid reabsorption were measured: proximal intratubular pressure (Pprox), early and late proximal flow rate, and early distal NaCl concentration. Pprox decreased by 0.5 +/- 0.1 mmHg, late proximal flow rate decreased by 2.0 +/- 0.8 nl/min, and early distal NaCl concentration decreased by 4.3 +/- 0.8 mM (mean +/- SE). No changes were observed after microperfusion with saline. Because the tubuloglomerular feedback mechanism was operating in the closed-loop mode, the decreased NaCl load to the macula densa will be compensated by an increase in the single-nephron glomerular filtration rate. In agreement with this, the early proximal flow rate, measured proximal 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 (approximately 36%). It is concluded that a decrease in local luminal angiotensin II levels and/or AT1 receptor activity under free flow conditions increases the rate of proximal tubular fluid reabsorption.
Leyssac
P P
PP
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
Karlsen
F M
FM
Holstein-Rathlou
N H
NH
D000042:Absorption / Q000187:drug effects; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001826:Body Fluids / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D019808:Losartan; D008297:Male; D010477:Perfusion; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D012965:Sodium Chloride; D019808:Losartan