Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 278, Issue 6, Pages F949-F953Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.2000.278.6.F949
Keywords
in vitro microperfusion; cytochrome P-450; omega-hydroxylase; hypertension; sodium-potassium-adenosinetriphosphatase; hydroxyeicosatetraenoic acids
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Funding
- NIDDK NIH HHS [DK-41612, DK-02232, P01 DK038226, DK-38226, R01 DK041612] Funding Source: Medline
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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 (J(v)) in the rabbit proximal straight tubule (PST). Production of 20- HETE by rabbit PST was demonstrated by incubating microdissected tubules with [H-3]arachidonic acid and separating the lipid extract by HPLC. There was significant conversion of [H-3]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 J(v). 19(S)-HETE in the bathing solution stimulated PST J(v) 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.
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