Endothelium-dependent relaxation to arachidonic acid in porcine coronary artery: Is there a fourth pathway?

A. J. Lonigro, N. L. Weintraub, C. A. Branch, A. H. Stephenson, L. McMurdo, R. S. Sprague

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Endothelium-dependent relaxations to bradykinin (BK) in U46619-contracted, indomethacin (INDO)-treated porcine coronary artery (PCA) rings are modestly attenuated by the nitric oxide (NO) synthase inhibitor, Nω-nitro-l-arginine methyl ester (L-NAME); whereas, when contracted with KCl, L-NAME abolishes BK relaxations. In contrast, endothelium-dependent arachidonic acid (AA) relaxations of U46619-contracted, INDO-treated PCA rings are not affected by L-NAME. AA does not relax KCl-contracted rings. Since BK is known to release AA, we postulated that the non-NO component of BK relaxation of the PCA is mediated by AA or an AA metabolite. Changes in tension of PCA rings to BK and AA were determined in the presence and absence of phospholipase (PLA), cyclooxygenase (CO), lipoxygenase (LO) and cytochrome P-450 (cP450) inhibitors. Responses to BK were attenuated by PLA inhibitors. No other inhibitors, however, eliminated responses to either BK or AA. The results suggest that relaxation to BK in PCA rings requires PLA activity, but relaxation to AA is independent of PLA, CO, LO or cP450 activity. We conclude that relaxation to BK and AA in the PCA is mediated by a product of an unidentified pathway of AA metabolism or by an unknown second messenger system resident within the endothelium and responsive to AA.

Original languageEnglish (US)
Pages (from-to)567-577
Number of pages11
JournalPolish Journal of Pharmacology
Volume46
Issue number6
StatePublished - 1994
Externally publishedYes

Keywords

  • 4-bromophenacyl bromide
  • 7-ethoxyresorufin
  • BW755c
  • bradykinin
  • clotrimazole
  • cytochrome P-450
  • endothelium-derived hyperpolarizing factor
  • nafazatrom
  • proadifen
  • quinacrine

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Lonigro, A. J., Weintraub, N. L., Branch, C. A., Stephenson, A. H., McMurdo, L., & Sprague, R. S. (1994). Endothelium-dependent relaxation to arachidonic acid in porcine coronary artery: Is there a fourth pathway? Polish Journal of Pharmacology, 46(6), 567-577.