CYP450 4A inhibition attenuates O2 induced arteriolar constriction in chronic but not acute Goldblatt hypertension. Microvasc Res 2009 Dec;78(3):442-6
Date
09/19/2009Pubmed ID
19761780Pubmed Central ID
PMC2784231DOI
10.1016/j.mvr.2009.09.002Scopus ID
2-s2.0-71549144756 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
We explored the role of 20-hydroxy-5Z, 8Z, 11Z, 14Z-eicosatetraenoic acid (20-HETE) in oxygen-induced vasoconstriction in a normal renin form of hypertension [the 1 kidney-1 clip Goldblatt hypertensive rat (1K1C)] and a high renin form of hypertension [the 2 kidney-1 clip Goldblatt hypertensive rat (2K1C)]. A silver clip was placed around the left renal artery of adult Sprague-Dawley males. The right kidney was removed in the 1K1C group and left intact in the 2K1C group. Arteriolar responses to elevation of O(2) concentration in the superfusion solution from 0% O(2) to 21% O(2) were determined in the in situ cremaster muscle before and after inhibition of cytochrome P450 4A omega-hydroxylase (CYP450 4A) with N-methyl-sulfonyl-12, 12-dibromododec-11-enamide (DDMS). Arteriolar constriction to elevated PO(2) was enhanced in the chronic 1K1C but not the acute 1K1C or 2K1C. DDMS eliminated O(2)-induced arteriolar constriction in the 9-week 1K1C, but had no effect in the 2-week 1K1C, and only partially inhibited O(2)-induced constriction of arterioles in the 4-week 2K1C rat. These findings indicate that although the CYP4A/20-HETE system contributes to arteriolar constriction in response to elevated PO(2) in the established stage of 1K1C renovascular hypertension, physiological alterations in other mechanisms are the primary determinants of O(2)-induced constriction of arterioles in the early and developing stages of 1K1C and 2K1C hypertension.
Author List
Kunert MP, Friesma J, Falck JR, Lombard JHMESH terms used to index this publication - Major topics in bold
AmidesAnimals
Arterioles
Chronic Disease
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Disease Models, Animal
Enzyme Inhibitors
Hydroxyeicosatetraenoic Acids
Hypertension, Renovascular
Male
Muscle, Skeletal
Nephrectomy
Oxygen
Rats
Rats, Sprague-Dawley
Sulfones
Vasoconstriction
