Abstract 10218: Angiotensin Type 1 Receptor Blockers Enhances H2O2-induced Coronary Collateral Vasodilatation and Improves Diabetes Mellitus-induced Microvascular Endothelial Dysfunction in Canine Native Coronary Collateral Microcirculation in Vivo
Background: We have previously demonstrated that endothelium-derived hydrogen peroxide (H2O2) plays an important role in canine coronary microcirculation in vivo. We examined whether angiotensin type 1 receptor blockers (ARB) enhanced H2O2-induced vasodilatation in canine coronary collateral microvessels in vivo and if so, whether such beneficial effects of ARB acutely improves coronary collateral vasodilatation in diabetes mellitus (DM).
Methods: Canine subepicardial native collateral small arteries (CSA, ≥100 μm) and arterioles (CA, <100 μm) were observed by an intravital microscope under cyclooxygenase blockade. Coronary CSA and CA were visually traced between left anterior descending arteries and left circumflex coronary arteries (LCX) with an injection of indocyanine green. Coronary vascular responses to endothelium-dependent (bradykinin 20 μg/kg/min, ic) and -independent (nitroprusside, 80 μg/min, ic) vasodilators were examined under the following 6 conditions (n=5 each); (i) control, (ii) ARB (olmesartan, 10 μg/kg/min, 10 min, ic), (iii) ARB+catalase (an enzyme that dismutates H2O2 into water and oxygen, 1000 U/ml, 10 min), (iv) ARB+L-NMMA (NO synthase inhibitor, 2 μmol/min for 20 min, ic)+catalase, (v) DM (alloxan 60 mg/ kg, iv, 1 week prior to study) and (vi) DM+ARB. Bradykinin was continuously and retrogradely infused into the diagonal branch of LCX.
Results: ARB significantly increased the bradykinin-induced coronary vasodilatation compared with control in both sized arteries (CSA 10±1 vs. 5±1%, CA 25±4 vs. 20±4%, both P < 0.01). ARB+catalase significantly reduced the vasodilatation in CA (10±2%, P < 0.01) but not in CSA (8±2%), whereas ARB+L-NMMA+catalase decreased the vasodilatation in both sized arteries (CSA 2±1%, CA 6±1%, both P < 0.01). DM significantly decreased the coronary vasodilatation compared with control in both sized arteries (CSA 1±1 vs. 5±1%, CA 7±2 vs. vs. 20±4%, both P < 0.01), whereas ARB improved the vasodilatation in both sized arteries (CSA 4±3%, CA 16±3%, both P < 0.01). Coronary vasodilatation to nitroprusside was comparable under all conditions.
Conclusions: ARB enhances H2O2-induced canine coronary collateral vasodilatation and improves microvascular endothelial function in DM in vivo.
- Coronary microcirculation
- Endothelium-derived relaxing factor
- Angiotensin II
- Nitric oxide
- Endothelial function
- © 2010 by American Heart Association, Inc.