Role of AT receptor in functional adaptation to ischemio-reperfusion in isolated rat hearts in relationship to oxidative stress

Implication of AT1 receptors (AT1R) in functional and metabolic modificatio ns associated with ischemia-reperfusion is not clearly defined. The aim of this study was:-to evaluate the role of AT1R in isolated rat hearts subject ed to a reversible ischemia; -to establish possible relationships between f unctional parameters and oxidative stress during reperfusion period. Isolated hearts perfused by the Langendorff method underwent 30 min of a gl obal total ischemia followed by 30 min of reperfusion. Functional parameter s and LDH release were recorded under AT1R stimulation by angiotensin II (A II) (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 o f reperfusion arrhythmia and LDH release. From the onset of reperfusion, a large and long lasting release of alkyl/alkoxyl radicals and glutathione wa s 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 ox idative stress intensity and AT1R activation, but these results couldn't ex clude the contribution of free radical in some myocardial effects of AT1R s timulation such as vasoconstriction and negative inotropic effect.