Contribution of NO and cytochrome P450 to the vasodilator effect of bradykinin in the rat kidney

David J Fulton, J. C. McGiff, J. Quilley

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Inhibition of nitric oxide generation with Nw‐nitro‐l‐arginine (nitroarginine) reduced vasodilator responses to bradykinin and acetylcholine and enhanced those to nitroprusside in the rat isolated perfused kidney, preconstricted with phenylephrine. Inhibition of cyclo‐oxygenase with indomethacin, decreased the vasodilator responses to bradykinin by ∼25% without affecting those to acetylcholine or nitroprusside. BW755c, a dual inhibitor of cyclo‐oxygenase and lipoxygenase, reduced renal vasodilator responses to bradykinin, comparable to the effect of indomethacin suggesting an effect related to inhibition of cyclo‐oxygenase rather than lipoxygenase. ETYA, an inhibitor of all arachidonic acid metabolic pathways, markedly reduced vasodilator responses to bradykinin but was without effect on the renal vasodilatation induced by acetylcholine or nitroprusside. Clotrimazole and 7‐ethoxyresorufin, inhibitors of cytochrome P450, greatly attenuated vasodilator responses to bradykinin without affecting those to acetylcholine or nitroprusside. These data suggest that the renal vasodilator response to bradykinin is subserved by arachidonic acid metabolites as well as nitric oxide, the former accounting for up to 70% of the vasodilator effect of bradykinin. 1992 British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)722-725
Number of pages4
JournalBritish Journal of Pharmacology
Volume107
Issue number3
DOIs
StatePublished - Jan 1 1992

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Bradykinin
Vasodilator Agents
Cytochrome P-450 Enzyme System
Kidney
Nitroprusside
Acetylcholine
Prostaglandin-Endoperoxide Synthases
Arachidonic Acid
Indomethacin
Nitric Oxide
5,8,11,14-Eicosatetraynoic Acid
4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine
Clotrimazole
Lipoxygenase Inhibitors
Lipoxygenase
Cyclooxygenase Inhibitors
Phenylephrine
Metabolic Networks and Pathways
Vasodilation

Keywords

  • NO synthesis inhibition
  • Rat perfused kidney
  • bradykinin‐induced vasodilatation
  • cytochrome P450 inhibitors
  • inhibition of arachidonate metabolism

ASJC Scopus subject areas

  • Pharmacology

Cite this

Contribution of NO and cytochrome P450 to the vasodilator effect of bradykinin in the rat kidney. / Fulton, David J; McGiff, J. C.; Quilley, J.

In: British Journal of Pharmacology, Vol. 107, No. 3, 01.01.1992, p. 722-725.

Research output: Contribution to journalArticle

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