Abstract 12648: Cardioprotection by Regular Ethanol Consumption is Mediated Through the Bradykinin B2 Receptor Through Increased Nitric Oxide Production
Introduction: We previously found chronic ethanol consumption induces cardioprotection against ischemia-reperfusion injury and is associated with increased expression of endothelial nitric oxide synthase (eNOS). Bradykinin has been implicated in ischemic preconditioning and has been shown to induce mitochondrial reactive oxygen species generation through nitric oxide (NO). We investigated the involvement of the bradykinin B2 receptor (BKB2R) and measured NO production in chronic ethanol-induced cardioprotection.
Methods: Isolated perfused hearts from control (CTL: n=8) and ethanol-treated (ETOH: n=8) guinea pigs were subjected to 30 min global ischemia and 120 min reperfusion. ETOH received 5% ethanol in their drinking water for 8 weeks. To determine whether BKB2R plays a role in chronic ethanol-induced cardioprotection, the BKB2R inhibitor, HOE-140 (100nM) was given for 15min prior to ischemia (ETOH+HOE: n=8, CTL+HOE: n=8). To investigate whether NO plays a role in ethanol-induced cardioprotection, a NOS inhibitor, L-NAME (100μM) was given upon reperfusion (ETOH+L-NAME: n=8). Contractile recovery was monitored by left ventricular developed and end-diastolic pressures (LVDP and LVEDP). Infarct size was determined by triphenyltetrazolium chloride staining. Nitric oxide in coronary effluent before ischemia and during reperfusion was measured by nitric oxide sensor.
Results: After ischemia-reperfusion, ETOH had significantly higher LVDP (61±6 vs. 26±3 mmHg), lower LVEDP (16±5 vs. 59±4 mmHg), and reduced infarct size (IS: 24±2 vs. 46±6%) compared to CTL (p<0.05). HOE-140 abolished chronic ethanol-induced cardioprotection (LVDP; 34±9 mmHg, LVEDP; 48±13 mmHg, infarct size: 45±11%). NO production during reperfusion was higher in ETOH than in CTL (133±19 vs. 44±6 nM, p<0.05, at 30 min reperfusion). HOE-140 abolished this increase in ETOH+HOE (70±11 nM). Administration of L-NAME during reperfusion abolished reduction of infarct size and increased NO production of ethanol-treated hearts. (Infarct sizeS:42.3±8 %, NO: 59±12 nM)
Conclusions: Chronic cardioprotection by regular ethanol consumption against ischemia-reperfusion injury is mediated through BKB2R and increased nitric oxide production.
- © 2010 by American Heart Association, Inc.