Cytochrome P450‐dependent effects of bradykinin in the rat heart

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

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Vasodilator responses to bradykinin (BK) in the rat heart are reported to be independent of NO and cyclo‐oxygenase/lipoxygenase products of arachidonic acid (AA). We verified that inhibition of NO synthase with l‐nitroarginine (50 μm) and cyclo‐oxygenase with indomethacin (2.8 μm) were without effect on vasodilator responses to BK (10–1000 ng) in the Langendorff rat heart preparation. l‐Nitroarginine elevated perfusion pressure, signifying a crucial role of NO in the maintenance of basal vasculature tone. In hearts treated with l‐nitroarginine to eliminate NO and elevate perfusion pressure, vasodilator responses were reduced by inhibitors of cytochrome P450 (P450), clotrimazole (1 μm) and 7‐ethoxyresorufin (1 μm). 17‐Octadecynoic acid (17‐ODYA 2 μm), a mechanism based inhibitor of P450‐dependent metabolism of fatty acids, also reduced vasodilator responses to BK. These results confirm that NO and prostaglandins do not mediate vasodilator responses to BK in the rat heart but suggest a major role for a P450‐dependent mechanism via AA metabolism. 1995 British Pharmacological Society

Original languageEnglish (US)
Pages (from-to)99-102
Number of pages4
JournalBritish Journal of Pharmacology
Volume114
Issue number1
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Bradykinin
Cytochromes
Vasodilator Agents
Prostaglandin-Endoperoxide Synthases
Perfusion
Arachidonate Lipoxygenases
Clotrimazole
Pressure
Arachidonic Acid
Nitric Oxide Synthase
Indomethacin
Cytochrome P-450 Enzyme System
Prostaglandins
Fatty Acids
Maintenance
Acids

Keywords

  • Rat perfused heart
  • cytochrome P450
  • nitric oxide
  • prostaglandins
  • vasodilatation to bradykinin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Cytochrome P450‐dependent effects of bradykinin in the rat heart. / Fulton, David J; Mahboubi, K.; McGiff, J. C.; Quilley, J.

In: British Journal of Pharmacology, Vol. 114, No. 1, 01.01.1995, p. 99-102.

Research output: Contribution to journalArticle

Fulton, David J ; Mahboubi, K. ; McGiff, J. C. ; Quilley, J. / Cytochrome P450‐dependent effects of bradykinin in the rat heart. In: British Journal of Pharmacology. 1995 ; Vol. 114, No. 1. pp. 99-102.
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