Renal V1A Receptor Does Not Increase Na+ Excretion in the Rat Isolated Kidney Perfused at Constant Pressure

Abstract

The effect of arginine vasopressin (AVP) on Na+ excretion has been the subject of many studies and is still a matter of debate. While AVP given at physiological doses was shown to enhance Na+ excretion in water‐loaded rats, others have shown that AVP‐induced natriuresis occurred at doses associated with increases in mean arterial pressure, suggesting that pressure natriuresis may be the underlying mechanism. This natriuresis is thought to be mediated by the V1A receptor (V1AR). To investigate if the renal V1AR mediates natriuresis, we employed the rat isolated kidney perfused at constant pressure to assess the effect of the selective V1AR agonist, [Phe2, Ile3, Orn8]‐vasopressin, on various parameters. Specifically, we sought to test the hypothesis that selective activation of V1AR in the kidney increases urinary excretion of Na+.Each isolated kidney was perfused for a total of 85 min, starting with 10 min for equilibration, and followed by five 15 min‐periods with ascending concentrations of the agonist (0, 30, 100, 300, and 1000 pM). Time‐control kidneys were perfused with media without the agonist for the entire 85 min.We found that the agonist increased renal vascular resistance in a concentration‐dependent manner without changing GFR. At the highest concentrations, the agonist showed antidiuretic activity characterized by decreased urine flow rate and effective water clearance, and increased urine osmolality. Our results further show that although there was an increase in absolute Na+ excretion and fractional excretion Na+, no difference was observed between treated‐ and control‐kidneys, suggesting that the changes in Na+ handling were inherent to perfusion itself rather than activation of the renal V1AR.We conclude that AVP‐induced natriuresis may not be mediated by the renal V1AR, and that AVP may induce natriuresis indirectly through extrarenal factors lacking in the isolated kidney.Support or Funding InformationFerring Research Institute, Inc., San Diego, CAThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.