Differential effect of cytochrome P-450 omega-hydroxylase inhibition on O2-induced constriction of arterioles in SHR with early and established hypertension. Microcirculation 2001 Dec;8(6):435-43
Date
01/10/2002Pubmed ID
11781816DOI
10.1038/sj/mn/7800114Scopus ID
2-s2.0-0000562293 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
OBJECTIVE: To determine whether two structurally and mechanistically different inhibitors of cytochrome P-450 omega-hydroxylase would alter the enhanced vasoconstrictor response to elevated PO2 in arterioles of spontaneously hypertensive rats (SHR). Cytochrome P-450 omega-hydroxylases, which catalyze the formation of the vasoconstrictor 20-hydroxyeicosatetraenoic acid from arachidonic acid, have been proposed to serve as microvascular O2 sensors.
METHODS: Arteriolar diameters were measured in the in situ cremaster muscle of 4- to 6- and 12- to 16-week-old SHR and normotensive Wistar-Kyoto (WKY) controls during superfusion with physiological salt solution (PSS) equilibrated with 0% O2 and 21% O2 before and after P-450 enzyme inhibition.
RESULTS: The P-450 omega-hydroxylase inhibitors 17-octadecynoic acid (17-ODYA) and N-methylsulfonyl-12, 12-dibromododec-11-enamide (DDMS) significantly reduced O2-induced constriction of arterioles of 12- to 16-week-old SHR and WKY and eliminated the difference in the response between the two groups. In contrast, both enzyme inhibitors attenuated the O2-induced constriction of arterioles in the younger WKY, but not in the 4- to 6-week-old SHR.
CONCLUSIONS: These results support the hypothesis that cytochrome P-450 4A may act as an O2 sensor in the skeletal muscle microcirculation and suggest that 20-hydroxyeicosatetraenoic acid plays an important role in the enhanced response to elevated PO2 in the SHR with established hypertension. Other mechanisms seem to contribute to the enhanced sensitivity of arterioles to elevated PO2 in young SHR during the early development of hypertension.
Author List
Kunert MP, Roman RJ, Falck JR, Lombard JHMESH terms used to index this publication - Major topics in bold
AmidesAnimals
Arterioles
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Dose-Response Relationship, Drug
Enzyme Inhibitors
Fatty Acids, Unsaturated
Hydroxyeicosatetraenoic Acids
Hypertension
Mixed Function Oxygenases
Oxygen
Rats
Rats, Inbred SHR
Sulfones
Vasoconstriction
