Modulation by cytochrome P450-4A ω-hydroxylase enzymes of adrenergic vasoconstriction and response to reduced PO₂ in mesenteric resistance arteries of Dahl salt-sensitive rats. Microcirculation 2010 Oct;17(7):525-35
Date
11/03/2010Pubmed ID
21040118Pubmed Central ID
PMC3057905DOI
10.1111/j.1549-8719.2010.00053.xScopus ID
2-s2.0-78649484453 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
OBJECTIVE: This study evaluated the contribution of the 20-HETE/cytochrome P450-4A ω-hydroxylase (CYP4A) system to the early development of salt-induced vascular changes in Dahl salt-sensitive (SS) rats.
METHODS: CYP4A expression and 20-HETE production were evaluated and responses to norepinephrine, endothelin, and reduced PO₂ were determined by video microscopy in isolated mesenteric resistance arteries from SS rats fed high salt (HS; 4% NaCl) diet for three days vs. low salt (LS; 0.4% NaCl) controls.
RESULTS: CYP4A enzyme inhibition with dibromododecenyl methylsulfimide (DDMS) selectively reduced norepinephrine sensitivity and restored impaired vasodilation in response to reduced PO₂ in SS rats fed HS diet. In the presence of DDMS, vasodilatation to reduced PO₂ was eliminated by indomethacin and unaffected by l-NAME in rats fed LS diet, and eliminated by l-NAME and unaffected by indomethacin in rats fed HS diet. The 20-HETE agonist WIT003 restored norepinephrine sensitivity in DDMS-treated arteries of HS-fed rats. HS diet increased vascular 20-HETE production and CYP4A protein levels by ∼24% and ∼31%, respectively, although these differences were not significant.
CONCLUSIONS: These findings support the hypothesis that the 20-HETE/CYP4A system modulates vessel responses to norepinephrine and vascular relaxation to reduced PO₂ in mesenteric resistance arteries of SS rats fed HS diet.
Author List
Raffai G, Wang J, Roman RJ, Anjaiah S, Weinberg B, Falck JR, Lombard JHMESH terms used to index this publication - Major topics in bold
AmidesAnimals
Cyclooxygenase Inhibitors
Cytochrome P-450 CYP4A
Endothelin-1
Enzyme Inhibitors
Hydroxyeicosatetraenoic Acids
Hypoxia
In Vitro Techniques
Indomethacin
Male
Mesenteric Arteries
Microscopy, Video
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Norepinephrine
Rats
Rats, Inbred Dahl
Sodium Chloride, Dietary
Sulfones
Vascular Resistance
Vasoconstriction