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

Author

Julian Lombard PhD, MS Emeritus Professor in the Physiology department at Medical College of Wisconsin

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