The CYP450 hydroxylase pathway contributes to P2X receptor-mediated afferent arteriolar vasoconstriction.

Academic Article

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.
  • Authors

    Keywords

  • 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
  • Digital Object Identifier (doi)

    Author List

  • Zhao X; Inscho EW; Bondlela M; Falck JR; Imig JD
  • Start Page

  • H2089
  • End Page

  • H2096
  • Volume

  • 281
  • Issue

  • 5