Activation of cardiac afferents by arachidonic acid: Relative contributions of the different metabolic pathways

S. Y. Sun, W. Wang, H. D. Schultz

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Arachidonic acid (AA) is metabolized by cyclooxygenase (COX), 5-lipoxygenase (5-LOX) and cytochrome P450 (P450) to produce a variety of bioactive products. The role of AA and its metabolites in the activation of cardiac afferents have not been investigated. This study aimed to examine the effects of exogenous AA on the activity of cardiac afferents and to evaluate the relative contributions of its three metabolic pathways in these effects. Single-unit activity of cardiac chemosensitive afferents was recorded from the cervical vagi in anesthetized rats, and their response to epicardial application of AA was measured with and without blockade of COX, 5-LOX and P450 respectively. The effects of some AA metabolites from the different pathways on the activity of cardiac afferents were also examined. AA (0.3-30 nmol) activated cardiac vagal afferents dose-dependently. Blockade of either COX (indomethacin, 5 mg/kg, iv) or P450 (17-octadecynoicacid, 1 mg/kg, iv), but not of 5-LOX (nordihydroguaiaretic acid, 5 mg/kg, iv), attenuated AA-induced activation of the cardiac afferents. Simultaneous blockade of COX and P450 totally blocked the activation evoked by AA. Among the tested metabolites from COX, PGE2, PGIZ and TXA2 activated cardiac afferents, while TXB2 and PGF, did not. 20-HETE and 14, 15-EET, the metabolites from P450 which were tested, also activated cardiac afferents. These data suggest that the AA-induced activation of cardiac vagal afferents is mediated by the metabolites from COX and P450, but not 5-LOX pathways in normal rats.

Original languageEnglish (US)
Pages (from-to)A689
JournalFASEB Journal
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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