Submitted on October 3, 2005
Accepted on December 27, 2005
Phenol injury-induced hypertension stimulates proximal tubule Na+/H+ exchanger activity
Patrick K.K. Leong1, Li E. Yang1, Carol S. Landon2, Alicia A. McDonough1, and Kay-Pong Yip2*
1 Department of Physiology & Biophysics, Universtiy of Southern California Keck School of Medicine, Los Angeles, CA, USA
2 Department of Physiology & Biophysics, University of South Florida, Tampa, FL, USA
* To whom correspondence should be addressed. E-mail: dyip{at}hsc.usf.edu.
Injection of 50 µl 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 (dpHi/dt) during luminal Na+ removal in PT pre-loaded with the pH-sensitive fluorescence dye BCECF. Injection of 50 µl 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 Na+/H+ exchanger activity, redistribution of NHE3 into low density apical membranes and hypertension. The increase in Na+/H+ exchanger activity may contribute to the lack of pressure-diuresis and the maintenance of chronic hypertension in this model.
