Faculty Collaboration Database

The CYP450 hydroxylase pathway contributes to P2X receptor-mediated afferent arteriolar vasoconstriction. Am J Physiol Heart Circ Physiol 2001 Nov;281(5):H2089-96

Date

10/23/2001

Pubmed ID

11668070

DOI

10.1152/ajpheart.2001.281.5.H2089

Scopus ID

2-s2.0-0035203299 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

This study was conducted to test the hypothesis that the cytochrome P-450 (CYP450) metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to the afferent arteriolar response to P2 receptor activation. Afferent arteriolar responses to ATP, the P2X agonist, alpha,beta-methylene ATP and the P2Y agonist UTP were determined before and after treatment with the selective CYP450 hydroxylase inhibitor, N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) or the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE). Stimulation with 1.0 and 10 microM ATP elicited an initial preglomerular vasoconstriction of 12 +/- 1% and 45 +/- 4% and a sustained vasoconstriction of 11 +/- 1% and 11 +/- 2%, respectively. DDMS or 20-HEDE significantly attenuated the sustained afferent arteriolar constrictor response to ATP. alpha,beta-Methylene ATP (1 microM) induced a rapid initial afferent vasoconstriction of 64 +/- 3%, which partially recovered to a stable diameter 10 +/- 1% smaller than control. Both DDMS and 20-HEDE significantly attenuated the initial vasoconstriction and abolished the sustained vasoconstrictor response to alpha,beta-methylene ATP. UTP decreased afferent diameter by 50 +/- 5% and 20-HEDE did not change this response. In addition, the ATP-induced increase in the intracellular Ca2+ concentration in preglomerular microvascular smooth muscle cells was significantly attenuated by 20-HEDE. Taken together, these results are consistent with the hypothesis that the CYP450 metabolite 20-HETE participates in the afferent arteriolar response to activation of P2X receptors.

Author List

Zhao X, Inscho EW, Bondlela M, Falck JR, Imig JD

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Amides
Animals
Arterioles
Aryl Hydrocarbon Hydroxylases
Enzyme Inhibitors
Hydroxyeicosatetraenoic Acids
Male
Muscle, Smooth, Vascular
Potassium Chloride
Rats
Rats, Sprague-Dawley
Receptors, Purinergic P2
Receptors, Purinergic P2X
Receptors, Purinergic P2Y1
Renal Artery
Sulfones
Uridine Triphosphate
Vasoconstriction