期刊
CIRCULATION JOURNAL
卷 76, 期 1, 页码 15-21出版社
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-11-1133
关键词
Aldehyde dehydrogenase; Cardiomyocytes; Cell death; Nitric oxide; Nitroglycerin tolerance
资金
- National Institute of Health [AA 11147, HL52141]
- Fundacao de Amparo a Pesquisa do Estado de Silo Paulo-Brasil (FAPESP) [2009/03143-1]
Acute myocardial infarction (MI) and its sequelae are leading causes of morbidity and mortality worldwide. Nitroglycerin (glyceryl trinitrate [GIN]) remains a first-line treatment for angina pectoris and acute MI. Nitroglycerin achieves its benefit by giving rise to nitric oxide (NO), which causes vasodilation and increases blood flow to the myocardium. However, continuous delivery of GTN results in tolerance, limiting the use of this drug. Nitroglycerin tolerance is caused, at least in part, by inactivation of aldehyde dehydrogenase 2 (ALDH2), an enzyme that converts GTN to the vasodilator, NO. We recently found that in a MI model in animals, in addition to GTN's effect on the vasculature, sustained treatment negatively affected cardiomyocyte viability following ischemia, thus resulting in increased infarct size. Coadministration of Alda-1, an activator of ALDH2, with GIN improves metabolism of reactive aldehyde adducts and prevents the GIN-induced increase in cardiac dysfunction following MI. In this review, we describe the molecular mechanisms associated with the benefits and risks of GTN administration in MI. (Circ J 2012; 76: 15-21)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据