Abstract 10892: Important Role of Endogenous Hydrogen Peroxide during Angiotensin Type 1 Receptor Blockers Administration in Pacing-Induced Metabolic Coronary Vasodilatation in Dogs in Vivo
Background: We have previously demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in canine coronary microcirculation in vivo. However, the role of H2O2/EDHF during angiotensin type 1 receptor blockers (ARB) administration in metabolic coronary vasodilatation in vivo remains to be examined. We examined whether H2O2 during ARB administration is involved in pacing-induced metabolic coronary vasodilatation in dogs in vivo and if so, whether such beneficial effects of ARB administration acutely improve coronary vasodilatation in diabetes mellitus (DM).
Methods: Canine subepicardial coronary small arteries (CSA, >100 µm) and arterioles (CA, <100 µm) in left anterior descending artery area were continuously observed by an intravital microscope under cyclooxygenase blockade (ibuprofen, 12.5 mg/kg, iv). Experiments were performed during paired right ventricular pacing under the following 6 conditions (n=5 each); (i) control, (ii) ARB (olmesartan, 10 μ g/kg/min, 10 min, ic), (iii) ARB +catalase (H2O2 decomposer, 1000 U/ml, 5 min, ic), (iv) DM (alloxan 40 mg/ kg, iv, 1 week prior to study), (v) DM+ARB and (vi) DM+ARB+catalase.
Results: Cardiac tachypacing (60 to 120 bpm) caused coronary vasodilatation in both-sized arteries under control conditions (CSA 5±1%, CA 14±1%). The metabolic coronary vasodilatation was significantly increased after ARB administration in both sized arteries (CSA 8±1% CA 19±4% vs. control, both P<0.05), whereas the response of ARB significantly decreased the vasodilatation of CA by catalase (CA 4±1%, vs. ARB, P<0.05), but not in CSA. DM significantly decreased the vasodilatation compared with control in CSA and there was a residual vasodilatation for the loss of NO in CA (CSA 1±1%, CA 10±2% vs. control, both P<0.05), whereas DM+ARB improved the vasodilatation compared with DM alone in both sized arteries (CSA: 4±1%, CA: 13±3% vs. DM, both p<0.05) and was significantly decreased by catalase in CA (CA: 5±2% vs. DM+ARB, p<0.05).
Conclusions: These results indicate that H2O2 during ARB administration is involved in pacing-induced metabolic coronary vasodilatation in DM in vivo and that there are substantial compensatory interactions between NO and H2O2.
- © 2011 by American Heart Association, Inc.