Role of endogenous hydrogen peroxide in cardiovascular ischaemia/reperfusion function: studies in mouse hearts with catalase-overexpression in the vascular endothelium.
Hydrogen peroxide (H2O2) has been implicated as a component of oxidative ischaemia/reperfusion stress. We investigated the role of H2O2 in cardiovascular ischaemia/reperfusion stress in hearts from mice overexpressing catalase in their endothelial cells. Hearts of transgenic (TG, n = 9) and age-matched wild-type (WT, n = 7) mice were perfused at constant flow (2.2 mlmin(-1)) and subjected to brief ischaemia and reperfusion. Intrinsic function and the effects of norepinephrine (3 nM-3 microM) were determined. Left ventricular pressure (LVDevP; balloon method), end-diastolic pressure (LVEDP), maximum rates of pressure development (+dP/dt, -dP/dt), coronary perfusion pressure (index of vascular function) and heart rate were recorded. Apart from a slightly higher recovery of LVDevP during reperfusion (+6 mmHg), neither systolic nor diastolic function was improved during ischaemia or reperfusion in TG hearts. However, hearts from TG mice exhibited a significantly better contractile response to noradrenergic stimulation (LVDevP: +20 mHg or 1.15-fold increase; +dP/dt: +1476 mmHgs(-1) or 1.2-fold increase) (P < 0.05). Norepinephrine relaxed the coronary microvasculature and increased heart rate, but no differences were detected between groups. We conclude that overexpressing catalase in endothelial cells is only weakly protective against myocardial or vascular ischaemia/reperfusion injury, but preserves the responsiveness of the heart to adrenergic stimulation.
Department of Pharmacology and Toxicology, Karl-Franzens-Universität, Universitätsplatz 2, A-8010 Graz, Austria.
Gerald
G
Wölkart
Gernot
G
Kaber
Georg
G
Kojda
Friedrich
F
Brunner
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D006861:Hydrogen Peroxide; D002374:Catalase; D007545:Isoproterenol; D009638:Norepinephrine