Phenol injury-induced hypertension stimulates proximal tubule Na+/H+ exchanger activity.
Injection of 50 microl 10% phenol into rat renal cortex activates renal sympathetic nerve activity which provokes acute hypertension that persists for weeks. We have previously shown with membrane fractionation that phenol injury caused a redistribution of the main proximal tubule (PT) apical transporter NHE3 (Na+/H+ exchanger isoform 3) to low density membranes enriched in apical microvilli. The aim of this study was to determine whether phenol injury increases PT apical Na+/H+ exchanger (NHE) activity. NHE activity was measured in vivo as the initial rate of change in intracellular pH (dpH(i)/dt) during luminal Na+ removal in PT preloaded with the pH-sensitive fluorescence dye BCECF. Injection of 50 microl 10% phenol increased blood pressure from 113 +/- 5.2 to 130 +/- 4.6 mmHg without changing glomerular filtration rate or urine output. NHE activity increased 2.6-fold by 70 min after phenol injury. The increase of NHE activity was accompanied with an increase of tubular reabsorption. Total NHE activity/NHE3 protein in cortical brush-border membrane (BBM) vesicles, measured by acridine orange quench and immunoblot, respectively, was unchanged by phenol injury. In conclusion, acute phenol injury provokes coincident increases in PT apical NHE activity, redistribution of NHE3 into low density apical membranes, and hypertension. The increase in NHE activity may contribute to the lack of pressure-diuresis and the maintenance of chronic hypertension in this model.
Leong
Patrick K K
PK
Dept. of Physiology and Biophysics, Univ. of Southern California Keck School of Medicine, Los Angeles, USA.
Yang
Li E
LE
Landon
Carol S
CS
McDonough
Alicia A
AA
Yip
Kay-Pong
KP
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D004231:Diuresis; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005919:Glomerular Filtration Rate; D006863:Hydrogen-Ion Concentration; D006977:Hypertension, Renal / Q000139:chemically induced*; D007668:Kidney / Q000294:innervation; D007672:Kidney Cortex / Q000187:drug effects; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D019800:Phenol / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000032:analysis / Q000378:metabolism*; D013564:Sympathetic Nervous System
D005452:Fluoresceins; D005456:Fluorescent Dyes; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D019800:Phenol; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein