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Am J Physiol Renal Physiol 283: F60-F67, 2002. First published February 12, 2002; doi:10.1152/ajprenal.00265.2001
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Vol. 283, Issue 1, F60-F67, July 2002

Cytochrome P-450 4A isoform expression and 20-HETE synthesis in renal preglomerular arteries

Jackleen S. Marji, Mong-Heng Wang, and Michal Laniado-Schwartzman

Department of Pharmacology, New York Medical College, Valhalla, New York 10595

20-Hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictor and mediator of the myogenic response, is a major arachidonic acid metabolite in the microvasculature of the rat kidney formed primarily by the cytochrome P-450 (CYP) 4A isoforms, CYP4A1, CYP4A2, and CYP4A3. We examined CYP4A isoform expression and 20-HETE synthesis in microdissected interlobar, arcuate, and interlobular arteries; mRNA for all CYP4A isoforms was identified by RT-PCR. Western blot analysis indicated that the levels of CYP4A2/4A3-immunoreactive protein increased with decreased arterial diameter, whereas those of CYP4A1-immunoreactive protein remained unchanged. 20-HETE synthesis was the highest in the interlobular arteries (17 ± 1.62 nmol · mg-1 · h-1) and, like CYP4A2/4A3-immunoreactive protein, decreased with increasing vessel diameter (4.5 ± 1.21, 2.65 ± 0.58, and 0.81 ± 0.14 nmol · mg-1 · h-1 in the arcuate, interlobar, and segmental arteries, respectively). 20-HETE synthesis in the renal artery and the abdominal aorta was undetectable. The observed decreased immunoreactivity of NADPH-cytochrome P-450 (c) oxidoreductase with increased arterial diameter provided a possible explanation for the decreased capacity to generate 20-HETE in the large arteries. The increase in CYP4A isoform expression and 20-HETE synthesis with decreasing diameter along the preglomerular arteries and the potent biological activity of 20-HETE underscore the significance of 20-HETE as a modulator of renal hemodynamics.

rat kidney; arachidonic acid; NADPH-cytochrome P-450 (c) oxidoreductase; hydroxyeicosatetraenoic acid


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