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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 
- and -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; -hydroxylase; hypertension; sodium-potassium-adenosinetriphosphatase; hydroxyeicosatetraenoic acids
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