Angiotensin II clamp prevents the second step in renal apical NHE3 internalization during acute hypertension

• Published in: American journal of physiology. Renal physiology 2002-11, Vol.283 (5), p.F1142-F1150
• Main Authors: Leong, Patrick K K, Yang, Li E, Holstein-Rathlou, Niels-Henrik, McDonough, Alicia A
• Format: Article
• Language: English
• Subjects: Acute Disease; Angiotensin II - pharmacology; Animals; Blood Pressure - physiology; Endosomes - metabolism; Feedback, Physiological - physiology; Glomerular Filtration Rate - physiology; Hypertension, Renal - metabolism; Male; Rats; Rats, Sprague-Dawley; Sodium - metabolism; Sodium-Hydrogen Exchanger 3; Sodium-Hydrogen Exchangers - metabolism; Sodium-Phosphate Cotransporter Proteins; Sodium-Phosphate Cotransporter Proteins, Type II; Symporters - metabolism; Vasoconstrictor Agents - pharmacology
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00178.2002

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.