[Role of AT1 receptors in functional adaptation to ischemia-reperfusion in solated rat hearts in relationship to oxidative stress].
Implication of AT1 receptors (AT1R) in functional and metabolic modifications associated with ischemia-reperfusion is not clearly defined. The aim of this study was:--to evaluate the role of AT1R in isolated rat hearts subjected to a reversible ischemia:--to establish possible relationships between functional parameters and oxidative stress during reperfusion period. Isolated hearts perfused by the Langendorff method underwent 30 min of a global total ischemia followed by 30 min of reperfusion. Functional parameters and LDH release were recorded under AT1R stimulation by angiotensin II (AII) (10(-7) M) and/or AT1R blockade by losartan (10(-6) M). Quantification of oxidative stress was performed in coronary effluents 1) directly, using ESR spectroscopy associated with PBN spin trapping and 2) indirectly, using HPLC method to detect glutathione (GSH + GSSG) release. Our results showed that All induced vasoconstrictive and negative inotropic effects during control period. During reperfusion. All reduced incidence of reperfusion arrhythmia and LDH release. From the onset of reperfusion, a large and long lasting release of alkyl/alkoxyl radicals and glutathione was detected and the intensity of the oxidative stress was not significantly changed in the groups treated will All and/or losartan. In conclusion, no relationship has been clearly demonstrated between the oxidative stress intensity and AT1R activation, but these results couldn't exclude the contribution of free radical in some myocardial effects of AT1R stimulation such as vasoconstriction and negative inotropic effect.
Oudot
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Laboratoire de physiopathologie et pharmacologie cardiovasculaires expérimentales, facultés de médecine et pharmacie, 7, bd Jeanne-d'Arc, BP 87900, 21079 Dijon.
Vergely
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C
Rochette
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D000222:Adaptation, Physiological; D000818:Animals; D005609:Free Radicals; D006321:Heart / Q000502:physiology*; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology*; D015425:Myocardial Reperfusion; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology*; D014661:Vasoconstriction
D005609:Free Radicals; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin