Role of 20-HETE in Elevating Loop Chloride Reabsorption in Dahl SS/Jr Rats

Abstract

Abstract In vivo tubular perfusion experiments were performed in normotensive Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats maintained from birth on a low salt (0.4% NaCl) diet to examine the role of 20-HETE in elevating loop Cl ⁻ transport in SS/Jr rats. Chloride reabsorption in the loop of Henle was significantly greater in SS/Jr than in SR/Jr rats (77±2% versus 57±3% of the perfused Cl ⁻ load). When the renal metabolism of arachidonic acid by P450 was blocked by the addition of 17-octadecynoic acid (10 μmol/L) to the perfusate, loop Cl ⁻ transport increased in SR/Jr rats to 70±2% of the delivered Cl ⁻ load, but it had no effect in SS/Jr rats. Conversely, addition of 20-HETE (10 μmol/L) to the perfusate lowered loop Cl ⁻ transport in S rats to 60±2% of perfused Cl ⁻ load, but it had no effect in SR/Jr rats. Addition of another endogenously formed HETE to the perfusate, 15-HETE (20 μmol/L), had no effect on Cl ⁻ reabsorption in the loop of Henle of SS/Jr rats. These findings indicate that endogenously produced P450 metabolites of arachidonic acid regulate Cl ⁻ transport in the loop of Henle of the rat in vivo and support the view that a diminished production of 20-HETE in the outer medulla of SS/Jr rats contributes to the elevation in loop Cl ⁻ transport and the resetting of the pressure-natriuresis relation in these animals.