Effects of high-salt diet on CYP450-4A ω-hydroxylase expression and active tone in mesenteric resistance arteries

Jingli Wang, Richard J. Roman, J R Falck, Lourdes De La Cruz, Julian H. Lombard

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

This study investigated the role of changes in the expression of the cytochrome P-450 4A (CYP450-4A) enzymes that produce 20-hydroxyeicosatetraenoic acid (20-HETE) in modulating the responses of rat mesenteric resistance arteries to norepinephrine (NE) and reduced Po2 after short-term (3-day) changes in dietary salt intake. The CYP450-4A2, -4A3, and -4A8 isoforms were all detected by RT-PCR in arteries obtained from rats fed a high-salt (HS, 4% NaCl) diet, whereas only the CYP450-4A3 isoform was detected in vessels from rats fed a low-salt (LS. 0.4% NaCl) diet. Expression of the 51-kDa CYP450-4A protein was significantly increased by a HS diet. Inhibiting 20-HETE synthesis with 30 μM N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) reduced the vasoconstrictor response to NE in arteries obtained from rats fed either a LS or HS diet, but NE sensitivity after DDMS treatment was significantly lower in vessels from rats on a HS diet. DDMS treatment also restored the vasodilator response to reduced Po2 that was impaired in arteries from rats on a HS diet. These findings suggest that 1) a HS diet increases the expression of CYP450-4A enzymes in the mesenteric vasculature, 2) 20-HETE contributes to the vasoconstrictor response to NE in mesenteric resistance arteries, 3) the contribution of 20-HETE to the vasoconstrictor response to NE is greater in rats fed a HS diet than in rats fed a LS diet, and 4) upregulation of the production of 20-HETE contributes to the impaired dilation of mesenteric resistance arteries in response to hypoxia in rats fed a HS diet.

Original languageEnglish (US)
Pages (from-to)H1557-H1565
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number4 57-4
DOIs
StatePublished - Apr 1 2005

Keywords

  • Cytochrome P-450
  • Hydroxyeicosatetraenoic acid
  • Hypertension
  • Isoform
  • Vascular bed

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Effects of high-salt diet on CYP450-4A ω-hydroxylase expression and active tone in mesenteric resistance arteries'. Together they form a unique fingerprint.

  • Cite this