Cumene hydroperoxide, an agent inducing lipid peroxidation, and 4-hydroxy-2,3-nonenal, a peroxidation product, cause coronary vasodilatation in perfused rat hearts by a cyclic nucleotide independent mechanism.
STUDY OBJECTIVE - The aim of the study was to determine whether cumene hydroperoxide, a substance known to induce lipid peroxidation through free radical action, and 4-hydroxy-2,3-nonenal (4-hydroxynonenal), a major aldehyde formed during lipid peroxidation, induce coronary vasodilatation by changing cyclic nucleotide levels. DESIGN - The study involved Langendorff perfused rat hearts, using different concentrations of cumene hydroperoxide and 4-hydroxynonenal, with sodium nitroprusside for comparison. Coronary flow was measured indirectly as retrograde aortic flow, with constant perfusion pressure. Information about the precise localisation of cyclic guanosine monophosphate (cGMP) in the heart was obtained by immunocytochemistry, using a new cGMP antiserum. EXPERIMENTAL MATERIAL - Hearts were from male Wistar rats, body weight 200-250 g. MEASUREMENTS and RESULTS - Both cumene hydroperoxide and 4-hydroxynonenal caused a dose dependent and reversible increase in coronary flow comparable with sodium nitroprusside. With sodium nitroprusside there was a good correlation between extent of vasodilatation and total heart cGMP concentration. Vasodilatation induced by cumene hydroperoxide or 4-hydroxynonenal was not accompanied by increase in total heart cGMP or cAMP (cyclic adenosine monophosphate) concentration. Isoprenaline was used as a positive control for cAMP. cGMP immunostaining was found in coronary vascular smooth muscle after vasodilatation with sodium nitroprusside, but no immunostaining was found in vascular smooth muscle after vasodilatation with cumene hydroperoxide or 4-hydroxynonenal. CONCLUSIONS - Cumene hydroperoxide and 4-hydroxynonenal can provoke reversible coronary vasodilatation in isolated perfused rat hearts by a cyclic nucleotide independent mechanism.
van der Kraaij
A M
AM
Department of Biochemistry I, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
de Jonge
H R
HR
Esterbauer
H
H
de Vente
J
J
Steinbusch
H W
HW
Koster
J F
JF
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D001783:Blood Flow Velocity / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects
D000447:Aldehydes; D001555:Benzene Derivatives; D000242:Cyclic AMP; D006152:Cyclic GMP; C027576:4-hydroxy-2-nonenal; D007545:Isoproterenol; C007164:cumene hydroperoxide