Different natriuretic responses in obese and lean rats in response to nitric oxide reduction

Am J Hypertens. 2011 Aug;24(8):943-50. doi: 10.1038/ajh.2011.79. Epub 2011 May 12.


Background: Nitric oxide (NO) is an important regulator of renal sodium transport and participates in the control of natriuresis and diuresis. In obesity, the nitric oxide bioavailability was reportedly reduced, which may contribute to the maintenance of hypertension. The aim of this study was to determine the effect of NO depletion on renal sodium handling in a model of diet-induced obesity hypertension.

Methods: Obese hypertensive (obesity-prone (OP)) and lean normotensive (obesity-resistant (OR)) Sprague-Dawley rats were treated with 1.2 mg/kg/day N(G)-nitro-L-arginine-methyl ester (L-NAME) for 4 weeks to inhibit NO synthesis. Acute pressure natriuresis and diuresis were measured in response to an increase in perfusion pressure. NHE3 and Na(+), K(+)-ATPase protein expression were measured by Western blot and NHE3 activity was determined as the rate of pH change in brush border membrane vesicles. NHE3 membrane localization was determined by confocal microscopy.

Results: L-NAME did not significantly attenuate the natriuretic and diuretic responses to increases in renal perfusion pressure (RPP) in OP rats while inducing a significant reduction in OR rats. Following chronic NO inhibition, NHE3 protein expression and activity and Na(+), K(+)-ATPase protein expression were significantly increased in the OR but not in the OP group. Immunofluorescence studies indicated that the increase in NHE3 activity could be, at least in part, due to NHE3 membrane trafficking.

Conclusions: Obese hypertensive rats have a weaker natriuretic response in response to NO inhibition compared to lean rats and the mechanism involves different regulation of the apical sodium exchanger NHE3 expression, activity, and trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Diuresis / drug effects*
  • Hypertension / physiopathology
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Natriuresis / drug effects*
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / metabolism
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers / metabolism*
  • Sodium-Potassium-Exchanging ATPase / metabolism


  • Slc9a3 protein, rat
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • Nitric Oxide
  • Sodium-Potassium-Exchanging ATPase
  • NG-Nitroarginine Methyl Ester