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
10/23/2001Pubmed ID
11668070DOI
10.1152/ajpheart.2001.281.5.H2089Scopus ID
2-s2.0-0035203299 (requires institutional sign-in at Scopus site) 45 CitationsAbstract
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 JDMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAmides
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