Role of 20-HETE in elevating chloride transport in the thick ascending limb of Dahl SS/Jr rats

Abstract

This study examined the role of endogenous 20 hydroxyeicosatetraenoic acid (20-HETE) in elevating Cl- transport in the medullary thick ascending loop of Henle (MTAL) of 9-week-old male Dahl salt-sensitive (SS/Jr) and salt- resistant (SR/Jr) rats perfused in vitro. Basal transepithelial voltage (V(te); 14.9±0.9 versus 10.1±0.5 mV) and net lumen-to-bath Cl- flux (J(Cl)) (155±6 versus 127±5 pEq · min-1 · m-1) were significantly greater in MTAL isolated from SS/Jr rats (n=16) than in those obtained from SR/Jr rats (n=16). Blockade of the synthesis of 20-HETE with 17-octadecynoic acid (17-ODYA; 10 μmol/L) increased V(te) from 9.9±0.8 to 13.1±1.0 mV and J(Cl) from 127±7 to 152±8 pEq · min-1 · mm-1 in the MTAL of SR/Jr rats (n=8), but it had no significant effect on V(te) or J(Cl) in the MTAL of SS/Jr rats (n=8). Exogenous 20-HETE (1 μmol/L) decreased V(te) from 14.8±0.6 to 10.5±0.6 mV and J(Cl) from 155±10 to 116±6 pEq · min-1 · mm-1 in MTAL of SS/Jr rats (n=8), but it had no effect on V(te) or J(Cl) in the MTAL of SR/Jr rats (n=8). The expression of P4504A2 protein in the MTAL of SS/Jr rats was approximately half of that seen in the MTAL of SR/Jr rats. These results indicate that endogenously formed 20-HETE regulates transepithelial voltage and Cl- transport in the MTAL and that a diminished production of 20-HETE contributes to an elevation in Cl- transport in the MTAL of SS/Jr rats.