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

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

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume283
Issue number1 52-1
StatePublished - Jul 4 2002
Externally publishedYes

Fingerprint

Cytochrome P-450 CYP4A
Renal Artery
Protein Isoforms
Arteries
Kidney
NADPH-Ferrihemoprotein Reductase
Proteins
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Abdominal Aorta
Vasoconstrictor Agents
Microvessels
Arachidonic Acid
Hemodynamics
Western Blotting
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Arachidonic acid
  • Hydroxyeicosatetraenoic acid
  • NADPH-cytochrome P-450 (c) oxidoreductase
  • Rat kidney

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Cytochrome P-450 4A isoform expression and 20-HETE synthesis in renal preglomerular arteries. / Marji, Jackleen S.; Wang, Mong-Heng; Laniado-Schwartzman, Michal.

In: American Journal of Physiology - Renal Physiology, Vol. 283, No. 1 52-1, 04.07.2002.

Research output: Contribution to journalArticle

@article{23c046893bcd401a8a07224fd8f7ffb3,
title = "Cytochrome P-450 4A isoform expression and 20-HETE synthesis in renal preglomerular arteries",
abstract = "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.",
keywords = "Arachidonic acid, Hydroxyeicosatetraenoic acid, NADPH-cytochrome P-450 (c) oxidoreductase, Rat kidney",
author = "Marji, {Jackleen S.} and Mong-Heng Wang and Michal Laniado-Schwartzman",
year = "2002",
month = "7",
day = "4",
language = "English (US)",
volume = "283",
journal = "American Journal of Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "1 52-1",

}

TY - JOUR

T1 - Cytochrome P-450 4A isoform expression and 20-HETE synthesis in renal preglomerular arteries

AU - Marji, Jackleen S.

AU - Wang, Mong-Heng

AU - Laniado-Schwartzman, Michal

PY - 2002/7/4

Y1 - 2002/7/4

N2 - 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.

AB - 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.

KW - Arachidonic acid

KW - Hydroxyeicosatetraenoic acid

KW - NADPH-cytochrome P-450 (c) oxidoreductase

KW - Rat kidney

UR - http://www.scopus.com/inward/record.url?scp=0036088707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036088707&partnerID=8YFLogxK

M3 - Article

VL - 283

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1931-857X

IS - 1 52-1

ER -