Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 284, Issue 2, Pages F313-F322Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00134.2002
Keywords
kidney; sympathetic nervous system; phenol; sodium/hydrogen exchanger type 3
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Funding
- NIDDK NIH HHS [DK-34316, DK-48522] Funding Source: Medline
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Renal injury-induced by phenol injection activates renal sympathetic afferent pathways, increases norepinephrine release from the posterior hypothalamus, activates renal efferent pathways, and provokes a rapid and persistent hypertension. This study aimed to determine whether phenol injury provoked a redistribution of proximal Na(+) transporters from internal stores to the apical cell surface mediated by sympathetic activation, a response that could contribute to generation or maintenance of hypertension. Anesthetized rats were cannulated for arterial blood pressure tracing and saline infusion and then 50 mul 10% phenol or saline was injected into one renal cortex (n = 7 each). Fifty minutes after injection, kidneys were removed and renal cortex membranes from injected kidneys were fractionated on sorbitol gradients and pooled into three windows (WI-WIII) that contained enriched apical brush border (WI); mixed apical, intermicrovillar cleft and dense apical tubules (WII); and intracellular membranes (WIII). Na(+) transporter distributions were determined by immunoblot and expressed as percentage of total in gradient. Acute phenol injury increased blood pressure 20-30 mmHg and led to redistribution of Na(+)/H(+) exchanger type 3 (NHE3) out of WIII (from 22.79 +/- 4.75 to 10.79 +/- 2.01% of total) to WI (13.07 +/- 1.97 to 27.15 +/- 4.08%), Na(+)-P(i) cotransporter 2 out of WII (68.72 +/- 1.95 to 59.76 +/- 2.21%) into WI (9.5 +/- 1.62 to 18.7 +/- 1.45%), and a similar realignment of dipeptidyl-peptidase IV immunoreactivity and alkaline phosphatase activity to WI. Renal denervation before phenol injection prevented the NHE3 redistribution. By confocal microscopy, NHE3 localized to the brush border after phenol injection. The results indicate that phenol injury provokes redistribution of Na(+) transporters from intermicrovillar cleft/ intracellular membrane pools to apical membranes associated with sympathetic nervous system activation, which may contribute to phenol injury-induced hypertension.
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