Role of 20-HETE in Elevating Chloride Transport in the Thick Ascending Limb of Dahl SS/Jr Rats

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 (Vte; 14.9+/-0.9 versus 10.1+/-0.5 mV) and net lumen-to-bath Cl- flux (JCl) (155+/-6 versus 127+/-5 pEq. min-1. mm-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 micromol/L) increased Vte from 9. 9+/-0.8 to 13.1+/-1.0 mV and JCl 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 Vte or JCl in the MTAL of SS/Jr rats (n=8). Exogenous 20-HETE (1 micromol/L) decreased Vte from 14.8+/-0.6 to 10.5+/-0.6 mV and JCl 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 Vte or JCl 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.