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

This study investigated the role of changes in the expression of the cytochrome P-450 4A (CYP45O-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-thy) changes in dietary salt intake. The CYP45O-4A2, -4A3, and -4A8 isoforms were all detected by RT-PCR in arteries obtained from rats fed a high-salt (HS, 4% NaC1) diet, whereas only the CYP45O-4A3 isoform was detected in vessels from rats fed a low-salt (LS, 0.4% NaC1) diet. Expression of the 51-kDa CYP45O-4A protein was significantly increased by a HS diet. Inhibiting 20-HETE synthesis with 30 μM N-methylsulfonyl-l2,l2-dibromododec-11-enamide (DDMS) reduced the vasoconstrictor response to NE in arteries obtained from rats fed either a IS 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 118 diet increases the expression of CYP45O-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-HEm 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. [ABSTRACT FROM AUTHOR]