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Am J Physiol Renal Physiol (February 12, 2002). doi:10.1152/ajprenal.00265.2001
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Articles in PresS, published online ahead of print February 12, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00265.2001
Submitted on August 20, 2001
Accepted on February 11, 2002

Cytochrome P450 4A Isoform Expression and 20-Hydroxyeicosatetraenoic Acid Synthesis in Renal Preglomerular Arteries

Jackleen S Marji1, Mong-Heng Wang1, and Michal Laniado-Schwartzman1*

1 Department of Pharmacology, New York Medical College, Valhalla, NY, USA

* To whom correspondence should be addressed. E-mail: Jackleen_Marji{at}nymc.edu.

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 P450 (CYP) 4A isoforms, 4A1, 4A2 and 4A3. 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 while those of CYP4A1-immunoreactive protein remained unchanged. 20-HETE synthesis was the highest in the interlobular arteries (17±1.62 nmol/mg/hr) 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/hr 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 P450 (c) reductase 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 20-HETE's potent biological activity underscore the significance of 20-HETE as a modulator of renal hemodynamics.




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