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Linoleic acid metabolites act to increase contractility in isolated rat heart

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Abstract

Previous in vivo studies in dogs suggest that the 9,10-monoepoxide of linoleic acid (9,10-cis-epoxyoctadecenoic acid [9,10-EOA]) has toxic cardiovascular effects that result in death at higher doses. More recent work with rabbit renal proximal tubule cells suggests that the 12,13-metabolites of linoleic acid are more toxic than the 9,10-isomers. Thus, in the current study, we tested the hypothesis that 12,13-EOA and 12,13-dihydroxyoctadecadienoic acid (12,13-DHOA) have direct adverse effects on the heart. Langendorff-perfused rat hearts were exposed to 30 μM linoleic acid, 30 μM 12,13-EOA, or 30 μM 12,13-DHOA for 60 min followed by a 30-min recovery period. As indicated by peak left intraventricular pressure and/or +dP/dtmax, all three of the agents elicited moderate increases in contractile function that peaked within 10–20 min. The effects of linoleic acid and 12,13-EOA returned to control values during the remainder of the 60-min exposure, whereas the positive inotropic response to 12,13-DHOA was maintained until washout. Sustained arrhythmias and negative inotropic actions were not observed with any of the three compounds. Subsequently, the monoepoxides were infused into conscious rats (35 mg/kg/h) while blood pressure, heart rate, and EKG were monitored for 24 h using biotelemetry techniques. The only effect observed was a slight decline in blood pressure. Thus, current data suggest that linoleic acid and its oxidative metabolites do not have direct cardiotoxic effects during acute exposure.

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Author notes

  1. David F. Grant

    Present address: Department of Pharmaceutical Sciences, University of Connecticut, 06269-2092, Storrs, CT

Authors and Affiliations

  1. Department of Pharmacology & Toxicology, University of Arkansas for Medical Sciences, 72205-7199, Little Rock, AR

    David F. Grant

  2. Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 W Markham Street, Mail Slot 522, 72205-7199, Little Rock, AR

    Lex A. Mitchell, Russell B. Melchert, Nathan M. Petty & Richard H. Kennedy Ph.D.

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Correspondence to Richard H. Kennedy Ph.D..

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Mitchell, L.A., Grant, D.F., Melchert, R.B. et al. Linoleic acid metabolites act to increase contractility in isolated rat heart. Cardiovasc Toxicol 2, 219–229 (2002). https://doi.org/10.1007/s12012-002-0006-3

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