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Am J Physiol Renal Physiol 278: F949-F953, 2000;
0363-6127/00 $5.00
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Vol. 278, Issue 6, F949-F953, June 2000

Effects of 20-HETE and 19(S)-HETE on rabbit proximal straight tubule volume transport

Raymond Quigley1, Michel Baum1,2, Komandla Malla Reddy3, James C. Griener1, and J. R. Falck3

Departments of 1 Pediatrics, 2 Internal Medicine, and 3 Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9063

The kidney has the highest abundance of cytochrome P-450 of all extrahepatic organs. Within the kidney, the highest concentration of cytochrome P-450 is found in the proximal tubule. Whether 20- or 19(S)-hydroxyeicosatetraenoic acid (HETE), the major P-450 metabolites of arachidonic acid in the proximal tubule, affect transport in this segment has not been previously investigated. We examined the direct effects of 20- and 19(S)-HETE on volume absorption (Jv) in the rabbit proximal straight tubule (PST). Production of 20-HETE by rabbit PST was demonstrated by incubating microdissected tubules with [3H]arachidonic acid and separating the lipid extract by HPLC. There was significant conversion of [3H]arachidonic acid to 20-HETE in control tubules that was inhibited by 10-5 M N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS). Addition of exogenous 20-HETE had no effect on PST volume transport. However, inhibition of endogenous production of 20-HETE using DDMS stimulated transport. In the presence of DDMS, 20-HETE inhibited PST Jv. 19(S)-HETE in the bathing solution stimulated PST Jv alone and in the presence of DDMS. Thus omega - and omega -1-hydroxylase products of arachidonic acid have direct effects on PST transport. Endogenous production of 20-HETE may play a role in tonic suppression of transport and may therefore be an endogenous regulator of transport in the proximal tubule.

in vitro microperfusion; cytochrome P-450; omega -hydroxylase; hypertension; sodium-potassium-adenosinetriphosphatase; hydroxyeicosatetraenoic acids


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