title: Angiotensin II clamp prevents the second step in renal apical NHE3 internalization during acute hypertension.
abstract: Acute hypertension inhibits proximal tubule (PT) sodium reabsorption. The resultant increase in NaCl delivery to the macula densa suppresses renin release. We tested whether the sustained pressure-induced inhibition of PT sodium reabsorption requires a renin-mediated decrease in ANG II levels. Plasma ANG II concentration of anesthesized Sprague-Dawley rats was clamped by simultaneous infusion of the ANG I-converting enzyme inhibitor captopril (12 microg/min) and ANG II (20 ng. kg(-1). min(-1)). Blood pressure was increased 50 mmHg for 20 min by arterial constriction +/- ANG II clamp or by sham operation. This acute hypertension increased urine output and endogenous Li(+) clearance, and these responses were blunted 40-50% in ANG II clamped rats. Acute hypertension provoked a rapid redistribution of Na(+)/H(+) exchanger isoform 3 (NHE3) out of apical brush-border membranes (21 +/- 4% decrease of total NHE3 abundance) to endosomal/lysosomal membranes (16 +/- 6% increase of total). In ANG II-clamped rats, acute hypertension also provoked disappearance of NHE3 from the apical membranes (27 +/- 2% decrease of total), but NHE3 was shifted to membranes enriched in intermicrovillar cleft and dense apical tubules (step 1) rather than endosomal/lysosomal membranes (step 2). This difference was independently confirmed by confocal analysis. In contrast, the pressure-induced redistribution of Na(+)-P(i) cotransporter type 2 was not altered by ANG II clamp. We conclude that the responses to acute hypertension, including diuresis and redistribution of PT NHE3 into intracellular membranes, require a responsive renin-angiotensin system and that the responses may be induced by the sustained increase in NaCl delivery to the macula densa during acute hypertension.
authors.affiliation: Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, Los Angeles, California 90089-9142, USA.
authors.forename: Patrick K K
authors.initials: PK
authors.lastname: Leong
authors.forename: Li E
authors.initials: LE
authors.lastname: Yang
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
authors.forename: Alicia A
authors.initials: AA
authors.lastname: McDonough
mesh_terms: D000208:Acute Disease; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D025461:Feedback, Physiological / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000502:physiology; D006977:Hypertension, Renal / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012964:Sodium