Increased proximal tubule NHE-3 and H+-ATPase activities in spontaneously hypertensive rats

Objective To investigate renal proximal tubular sodium-hydrogen exchanger 3 (NHE-3) and H+-ATPase activities in young (5-week-old) spontaneously hyper tensive rats (SHR) and normotensive Donryu (DRY) rats, in the period during which high blood pressure is developing. Methods Five-week-old SHR and DRY rats were weighed and systolic blood pres sure recorded. Proximal tubule cells were isolated, loaded with the intrace llular pH dye, 2'-7'-bis-carboxyethyl-5(6)-carboxyfluorescein-acetoxymethyl -ester and acidified with a NH4+/NH3 prepulse. Na+-independent intracellula r pH recovery rate (H+-ATPase activity) and initial Naf-dependent intracell ular pH recovery rate (NHE-3 activity) were assessed. NHE-3 activity was as sessed during inhibition of H+-ATPase with Bafilomycin A(1) and during inhi bition of any possible NHE-1 activity with Hoe 694. Results Mean body weight and systolic blood pressures of 5-week-old SHR and DRY rats were not significantly different. NHE-3 activity was higher in SH R, 1.08 +/- 0.1 pH units/min compared with DRY rats, 0.73 +/- 0.1 pH units/ min (P < 0.05) H+-ATPase activity was also higher in SHR, 0.119 +/- 0.02 pH units/min, compared with DRY rats, 0.051 +/- 0.02 pH units/min (P< 0.05). Conclusions Proximal tubule cells of 5-week-old SHR have higher NHE-3 and H +-ATPase activities compared with age-matched DRY rats. Enhanced proximal t ubular fluid reabsorption is likely to contribute to development of high bl ood pressure in young SHR. I Hypertens 2000, 18:623-628 (C) Lippincott Will iams & Wilkins.