title: Effect of angiotensin II receptor blockade on proximal tubular fluid reabsorption.
abstract: 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.
authors.affiliation: Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
authors.forename: P P
authors.initials: PP
authors.lastname: Leyssac
authors.forename: F M
authors.initials: FM
authors.lastname: Karlsen
authors.forename: N H
authors.initials: NH
authors.lastname: Holstein-Rathlou
mesh_terms: 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
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D012965:Sodium Chloride; D019808:Losartan