Relaxation of porcine coronary artery to bradykinin role of arachidonic acid

Neal L. Weintraub, Shobha N. Joshi, Carrie A. Branch, Alan H. Stephenson, Randy S. Sprague, Andrew J. Lonigro

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Bradykinin-induced relaxation of precontracted, porcine coronary artery (PCA) rings is mediated by distinctly different endothelium-derived relaxing factors depending on the contractile agent used. Thus when contracted with KC1, bradykinin-induced relaxation of PCA rings is mediated solely by nitric oxide (NO), whereas when contracted with the thromboxane mimetic U46619, a small component of the relaxation is attributable to NO and a large component is attributable to a non-NO mechanism that is independent of cyclooxygenase activity. We hypothesized that the non-NO component was mediated by arachidonic acid (AA) or by a non-cyclooxygenase product of AA metabolism. Bradykinininduced relaxations of PCA rings precontracted with U46619 in the presence of indomethacin (10 /imol/L) were moderately attenuated by the NO synthase inhibitor W-nitro-L-arginine methyl ester (L-NAME, 100 fxmolfL), whereas when precontracted with KC1, L-NAME abolished the relaxations. AA produced endothelium-dependent relaxations of rings precontraded with U46619 that were unaffected by L-NAME, whereas AA did not relax rings precontracted with KC1. In rings precontracted with U46619, in the presence of L-NAME and indomethacin the phospholipase inhibitors quinacrine (50 fimolfL) and 4-bromophenacyl bromide (10 jtmol/L) attenuated bradykinin- but not AA-induced relaxations. Inhibitors of both lipoxygenase (BW 755c [100 /imol/L] and nafazatrom [20 /xmol/L]) and cytochrome P-450 (proadifen [10 iimol/L] and clotrimazole [10 /xmol/L]) pathways did not eliminate bradykinin- or AA-induced relaxations, although clotrimazole partially attenuated AA-induced relaxations. These findings suggest that bradykinin-induced relaxation of PCA rings is mediated by AA through a mechanism that is not dependent on cyclooxygenase, lipoxygenase, or cytochrome P-450 pathways.

Original languageEnglish (US)
Pages (from-to)976-981
Number of pages6
JournalHypertension
Volume23
Issue number6
DOIs
StatePublished - Jun 1994
Externally publishedYes

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Keywords

  • Arachidonic acid
  • Bradykinin
  • Coronary artery
  • Endothelium-derived relaxing factor

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Weintraub, N. L., Joshi, S. N., Branch, C. A., Stephenson, A. H., Sprague, R. S., & Lonigro, A. J. (1994). Relaxation of porcine coronary artery to bradykinin role of arachidonic acid. Hypertension, 23(6), 976-981. https://doi.org/10.1161/01.HYP.23.6.976