Dose/response curves of lipoic acid R-and S-forms in the working rat heart during reoxygenation: superiority of the R-enantiomer in enhancement of aortic flow.
Micromolar concentrations of lipoic acid racemate added to a working rat heart during hypoxia have been previously found to improve aortic flow during subsequent reoxygenation. Since the R-form represents the naturally occurring form of lipoic acid, and the S-form does not reveal a positive influence on ATP synthesis in isolated mitoplasts, a dose/response curve of both enantiomers has been performed in working rat hearts. After the end of perfusion mitochondria were isolated and further analysed. At a concentration of 0.05-0.1 mumol of the R-enantiomer, aortic flow rises precipitously during reoxygenation, reaching over 70% of normoxic values compared to 50% of the controls. By contrast, with the S-enantiomer a value of about 60% is attained at 1 mumol, only. Accordingly, ATPase activity in mitochondria isolated from rat hearts previously treated with 0.05-0.1 mumol of the R- or S-enantiomer was significantly decreased or increased respectively. Consequently, whereas mitochondrial ATP synthesis was increased when the R-enantiomer was previously added to the working heart at 0.05-0.1 mumol concentration, with the S-enantiomer ATP synthesis remained within the control range. Mitochondrial membrane fluidity, measured with diphenylhexatriene, revealed a trend towards increase with the R- and decrease with the S-enantiomer. The total amount of thiol added at 0.1 mumol concentration is consistent with a value of 2 nmol/mg mitochondrial protein. This value has previously been found to be connected with -SH groups which add oligomycin-sensitivity to the ATPase complex. It is suggested that oligomycin-sensitive mitochondrial -SH groups contribute to the overall efficiency of low concentrations of lipoic acid R-enantiomer to enhance aortic flow.
Gustav-Embden-Zentrum, Biologischen Chemie, Universitätsklinikum, Frankfurt am Main, Germany.
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Zimmer
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Beikler
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Schneider
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Ibel
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Tritschler
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Ulrich
D000251:Adenosine Triphosphatases / Q000032:analysis; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000503:physiopathology; D008297:Male; D008929:Mitochondria, Heart; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013237:Stereoisomerism; D008063:Thioctic Acid / Q000494:pharmacology*
D008063:Thioctic Acid; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D010100:Oxygen