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

The kidney has the highest abundance of cytochrome P-450 of all extrahepati c organs. Within the kidney, the highest concentration of cytochrome P-450 is found in the proximal tubule. Whether 20- or 19(S)-hydroxyeicosatetraeno ic acid (HETE), the major P-450 metabolites of arachidonic acid in the prox imal tubule, affect transport in this segment has not been previously inves tigated. We examined the direct effects of 20- and 19(S)-HETE on volume abs orption (J(v)) in the rabbit proximal straight tubule (PST). Production of 20- HETE by rabbit PST was demonstrated by incubating microdissected tubule s with [H-3]arachidonic acid and separating the lipid extract by HPLC. Ther e 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 vol ume transport. However, inhibition of endogenous production of 20- HETE usi ng DDMS stimulated transport. In the presence of DDMS, 20- HETE inhibited P ST J(v). 19(S)-HETE in the bathing solution stimulated PST J(v) alone and i n the presence of DDMS. Thus omega- and omega-1-hydroxylase products of ara chidonic acid have direct effects on PST transport. Endogenous production o f 20- HETE may play a role in tonic suppression of transport and may theref ore be an endogenous regulator of transport in the proximal tubule.