Abstract 12044: Hydrogen Sulfide Mediates Cardioprotection by Oral Ingestion of Beetroot Juice against Myocardial Infarction and Left Ventricular Dysfunction following Ischemia/Reperfusion
Background: Ingestion of high dietary nitrate in the form of beetroot juice (BRJ) has been shown to exert anti-hypertensive effects in humans through cGMP. Since cGMP-dependent signaling protects against ischemia/reperfusion (I/R) injury through upregulation of hydrogen sulfide (H2S), we hypothesized that BRJ may render such cardioprotection via H2S generation.
Methods and Results: Adult male CD-1 mice were given BRJ extract dissolved in drinking water at concentration of 10 g/L (containing ∼0.7 mM nitrate). Seven days later, the hearts were explanted for molecular analyses. A subset of mice was subjected to I/R injury by occlusion of the left coronary artery for 30 min and reperfusion for 24 h. The H2S producing enzyme, cystathionine-γ-lyase (CSE) specific inhibitor, dl-propargylglycine (PAG, 50 mg/kg, i.p.) was given 30 min before ischemia in the BRJ-pretreated mice. At the end of reperfusion, left ventricular (LV) function was assessed with echocardiography and myocardial infarct size was measured using tetrazolium chloride staining. BRJ ingestion significantly reduced infarct size and preserved LV fractional shortening as compared with controls (Fig. A & B; Mean±SE). PAG blocked the infarct-limiting cardioprotective effect of BRJ. Cardiac H2S level was significantly increased with BRJ intake (Fig. C). Quantitative PCR and Western blot analysis showed improvement in the levels of CSE mRNA and protein in the heart tissue with BRJ (Fig. D), whereas the mRNA level of another H2S producing enzyme, cystathionine β-synthase, remained unchanged.
Conclusion: BRJ reduces myocardial infarction and LV dysfunction following I/R. This cardioprotection is dependent upon CSE-mediated H2S generation. Modulation of endogenous H2S with regular intake of BRJ may be a novel, natural, inexpensive and safe therapeutic strategy to reduce I/R injury in patients with cardiovascular diseases.
- © 2012 by American Heart Association, Inc.