Abstract 11181: Angiotensin Type 1 Receptor Blocker Enhances H2O2-induced Coronary Collateral Vasodilatation and Improves Diabetes-induced Microvascular Endothelial Dysfunction and H2O2 Production during Acute Coronary Occlusion in Canine Coronary Native Collateral Microcirculation in vivo
Background: We examined whether an angiotensin type 1 receptor blocker (ARB) enhances hydrogen peroxide (H2O2, endothelium-derived hyperpolarizing factor)-induced vasodilatation and production during acute coronary occlusion in canine coronary collateral microvessels in vivo and if so, whether ARB acutely improves coronary collateral vasodilatation and endothelial H2O2 production in diabetes mellitus (DM).
Methods: Canine subepicardial native collateral small arteries (CSA >100 µm) and arterioles (CA <100 µm) were continuously observed by an intravital microscope under cyclooxygenase blockade. Experiments were performed during LAD ischemia (90 min) under the following 6 conditions (n=5 each); (i) control, C, (ii) ARB (olmesartan, 10 μ g/kg/min, ic)+L-NMMA (NOS inhibitor, 2 µmol/min, ic), AL, (iii) ARB +L-NMMA+apamin+charybdotoxin (both are inhibitors of Ca-activated K (KCa) channels, 1µmol/L and 100nmol/L, ic), ALAC, (iv) DM (alloxan 40 mg/kg iv, 1 week prior to study) (v) DM+ARB+L-NMMA, DAL, and (vi) DM+ARB+L-NMMA+apamin+charybdotoxin, DALAC. Bradykinin was continuously and retrogradely infused into the diagonal branch of LCX during myocardial ischemia (85min). H2O2 in myocardium was determined by quantitative measurement with an Amplex Red by ELISA.
Results:Myocardial ischemia in C caused significant vasodilatation by bradykinin in CA (7±1%) but not in CSA (-2±1%). After AL, the vasodilatation was significantly increased in CA (15±5%) compared with C, and was significantly decreased by ALAC in CA (-6±6%). DM significantly decreased the coronary vasodilatation compared with C in both-sized arteries (CSA 2±1%, CA -8±1%), whereas DAL significantly improved the vasodilatation compared with DM in CSA (7±2%) and was significantly decreased by DALAC in CA (-7±1%). H2O2 production (µmol/L/mg protein) in DAL was significantly increased compared with C, AL and DM and was significantly decreased by catalase. DAL ameliorated myocardial injury compared with DM, as assessed by myocardial troponin-I, respectively.
Conclusions:ARB enhances H2O2-mediated dilatation of canine coronary collateral arterioles and improves collateral vasodilatation, H2O2 production and myocardial injury in DM during coronary occlusion in vivo.
- Coronary microcirculation
- Endothelium-derived relaxing factor
- Collateral circulation
- Myocardial infarction
- Nitric oxide
- © 2012 by American Heart Association, Inc.