Mechanism of action of arachidonic acid in the isolated perfused rat heart

J. E. Shaffer, Kafait Malik

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The purpose of this study was to elucidate the mechanism of action of arachidonic acid in the isolated rat heart perfused with Krebs solution at a constant flow. Administration of arachidonic acid, 3.3-33 nmol, into the heart caused a small transient increase followed by a pronounced decrease in coronary perfusion pressure and increased myocardial tension, heart rate, and the output of prostaglandins (6-keto-PGF1(α), PGE2, and PGF2(α)). Administration of structurally similar fatty acids, dihomo-γ-linolenic acid, and 8,14,17-eicosatrienoic acid, produced vasoconstriction and decreased myocardial tension without affecting heart rate or the output of prostaglandins. Infusion of PGI2, PGF2(α), or PGE2 produced coronary vasodilation and increased myocardial tension, whereas PGF2(α) increased heart rate, an effect which was not prevented by propranolol. Indomethacin blocked the effect of arachidonic acid on myocardial tension and heart rate, but only reduced the duration of coronary vasodilation. The initial component of arachidonic acid induced coronary vasodilation which was unaffected by indomethacin and also remained unaltered during the infusion of three structurally dissimilar lipoxygenase inhibitors, eicosatetraynoic acid, nordihydroguaiaretic acid, and 1-phenyl-3-pyrazolidone. Indomethacin did not alter the effects of the exogenously administered prostaglandins on perfusion pressure or myocardial tension; however, it blocked the effect of PGF2(α) on heart rate. The effect of arachidonic acid or PGF2(α) to increase heart rate was not blocked by thromboxane synthetase inhibitors, imidazole, or OKY-1581. We conclude that the cardiac effects of arachidonic acid are mediated primarily through its conversion to cyclooxygenase products. However, the initial biphasic component of the coronary vascular response, vasoconstriction, and subsequent vasodilation produced during the first 3-min period following arachidonic acid administration appears to be unrelated to prostaglandins, whereas the duration of the coronary vasodilation depends upon the formation of cyclooxygenase products.

Original languageEnglish (US)
Pages (from-to)551-558
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Volume62
Issue number5
DOIs
StatePublished - Jan 1 1984

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Arachidonic Acid
Dinoprost
Vasodilation
Heart Rate
Prostaglandins
Indomethacin
Prostaglandin-Endoperoxide Synthases
Vasoconstriction
Dinoprostone
Perfusion
Thromboxane-A Synthase
Masoprocol
Pressure
Lipoxygenase Inhibitors
Acids
alpha-Linolenic Acid
Epoprostenol
Propranolol
Blood Vessels
Fatty Acids

All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology
  • Physiology (medical)

Cite this

Mechanism of action of arachidonic acid in the isolated perfused rat heart. / Shaffer, J. E.; Malik, Kafait.

In: Canadian Journal of Physiology and Pharmacology, Vol. 62, No. 5, 01.01.1984, p. 551-558.

Research output: Contribution to journalArticle

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