Faculty Collaboration Database

Effects of high-salt diet on CYP450-4A omega-hydroxylase expression and active tone in mesenteric resistance arteries. Am J Physiol Heart Circ Physiol 2005 Apr;288(4):H1557-65

Date

12/04/2004

Pubmed ID

15576442

DOI

10.1152/ajpheart.00755.2004

Scopus ID

2-s2.0-15744386940 (requires institutional sign-in at Scopus site)   38 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 Po(2) 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 muM 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 Po(2) 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.

Author List

Wang J, Roman RJ, Falck JR, de la Cruz L, Lombard JH

MESH terms used to index this publication - Major topics in bold

Amides
Animals
Blood Pressure
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Enzyme Inhibitors
Hydroxyeicosatetraenoic Acids
Male
Mesenteric Arteries
Mixed Function Oxygenases
Norepinephrine
RNA, Messenger
Rats
Rats, Sprague-Dawley
Sodium Chloride, Dietary
Sulfones
Vascular Resistance
Vasoconstrictor Agents