title: Linoleic acid metabolites act to increase contractility in isolated rat heart.
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 microM linoleic acid, 30 microM 12,13-EOA, or 30 microM 12,13-DHOA for 60 min followed by a 30-min recovery period. As indicated by peak left intraventricular pressure and/or +dP/dt(max), 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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Kansas for Medical Sciences, Little Rock, AR 72205-7199, USA.
authors.forename: Lex A
authors.initials: LA
authors.lastname: Mitchell
authors.forename: David F
authors.initials: DF
authors.lastname: Grant
authors.forename: Russell B
authors.initials: RB
authors.lastname: Melchert
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Petty
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009829:Oleic Acids / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C425204:12,13-dihydroxyoctadecenoic acid; C119104:12,13-epoxy-9-octadecenoic acid; D009829:Oleic Acids; D019787:Linoleic Acid