(Hypertension. 1999;33:419-423.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Role of 20-HETE in Elevating Chloride Transport in the Thick Ascending Limb of Dahl SS/Jr Rats
From the Department of Physiology, Medical College of Wisconsin, Milwaukee.
Correspondence to Richard J. Roman, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail rroman{at}post.its.mcw.edu
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 (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 µmol/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 µmol/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.
Key Words: kidney • sodium • potassium • ion transport • cytochrome P450 • hypertension, salt-sensitive • blood pressure
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