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 hypertensive 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 pressure recorded. Proximal tubule cells were isolated, loaded with the intracellular pH dye, 2'-7'-bis-carboxyethyl-5(6)-carboxyfluorescein-acetoxymethyl-ester and acidified with a NH4+/NH3 prepulse. Na+-independent intracellular pH recovery rate (H+-ATPase activity) and initial Na+-dependent intracellular pH recovery rate (NHE-3 activity) were assessed. NHE-3 activity was assessed during inhibition of H+-ATPase with Bafilomycin A1 and during inhibition 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 SHR, 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 tubular fluid reabsorption is likely to contribute to development of high blood pressure in young SHR.
Aldred
K L
KL
The Department of Physiology, The University of Melbourne, Parkville, Australia.
Harris
P J
PJ
Eitle
E
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001794:Blood Pressure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D018942:Macrolides; D008297:Male; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D018942:Macrolides; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases