title: Oxidative injury to myocardial membrane: direct modulation by endogenous alpha-tocopherol.
abstract: Peroxidation of myocardial-membrane phospholipid is considered an important pathogenic component of heart muscle damage in ischemia and reperfusion. The extent to which membrane alpha-tocopherol (vitamin E) in the heart can modulate such damage and protect against it is a matter of controversy. The relative alpha-tocopherol deficit of spontaneously-hypertensive (SH) rat myocardium as compared to the myocardium of the Wistar-Kyoto (W/K) normotensive parent strain prompted use of these animals to identify and characterize any protective antiperoxidant role of endogenous, myocardial-membrane alpha-tocopherol. With exposure to a superoxide- and iron-containing initiator of peroxidation, the membrane complements from the ventricular myocardia of the SH rat and the W/K parent strain were found to have very different peroxidative-injury profiles. SH-rat myocardial membrane demonstrated a marked sensitivity to peroxidation as reflected in the acute onset and rapid progression of phospholipid damage. The greater susceptibility of SH-rat myocardial membrane to free-radical attack could not be explained by inter-strain compositional differences in membrane polyunsaturated fatty acids or fatty aldehydes. Rather, the basis for the enhanced peroxidation was identified as the 3-fold lower alpha-tocopherol content of SH-rat myocardial membrane with respect to the heart-muscle membrane from the normotensive animal. The relative alpha-tocopherol deficit not only increased the susceptibility of SH-rat cardiac membrane to damage under pro-oxidant conditions, but also reduced the efficacy of exogenously supplied antioxidant intervention. These findings demonstrate that membrane alpha-tocopherol tone is a critical protectant of myocardial phospholipid against oxidative injury and acts as a determinant of the course of heart-membrane peroxidative damage.
authors.affiliation: Department of Pharmacology and Chemotherapy, Hoffmann-La Roche Inc., Nutley, NJ 07110.
authors.forename: D R
authors.initials: DR
authors.lastname: Janero
authors.forename: B
authors.initials: B
authors.lastname: Burghardt
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation; D008081:Liposomes; D008563:Membrane Lipids / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000235:genetics / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*; D011921:Rats, Inbred WKY / Q000235:genetics / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000633:toxicity; D014810:Vitamin E / Q000502:physiology*; D014811:Vitamin E Deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008081:Liposomes; D008563:Membrane Lipids; D010743:Phospholipids; D013481:Superoxides; D014810:Vitamin E; D007501:Iron; D013482:Superoxide Dismutase