Mechanisms of Renal Injury Induced Chronic Hypertension

Li E. Yang, S. H. Ye, P. K.K. Leong, V.M. Campese, A. A. McDonough
Department of Physiology and Biophysics
University of Southern California, Keck School of Medicine
Los Angeles, CA 90089-9142

Abstract

Minimal phenol injury to kidney (inj. 50 µl 10% phenol = PhI) leads to acute hypertension (30 min) that persists (5 wks), mediated by SNS activation and renal afferents. We have reported that acute response involves NHE3 recruitment from intracellular (IC) pools to the PT apical microvilli (AMV) where it could increase Na+ retention and contribute to hypertension.

Aim.
Determine if proximal tubule (PT) Na+ transporter distribution and/or pool size are altered chronically by PhI. Rat kidneys were studied 5 weeks after PhI or sham control (SC) by subcellular fractionation and confocal microscopy.

Results:
Blood pressure increased to 132 ± 3 mmHg in PhI vs. 115 ± 3 in SC; NHE3 distribution shifted to AMV (23.9 ± 3% in PhI vs.12.7 ± 3% in SC), from IC pools (9.7 ± 1% in PhI vs. 18.9 ± 3% in SC). Alkaline phosphotase activity increased 45% in AMV. Cortex NHE3 pool size decreased 42.2 ± 4%.

Conclusion:
Shifts in % NHE3 to AMV may contribute to persistent hypertension after PhI; decrease in NHE3 pool size at 5 weeks may be compensatory response to hypertension per se. DK34316, AHA Western States.