Nitrite consumption in ischemic rat heart catalyzed by distinct blood-borne and tissue factors

Abstract

Nitrite consumption in ischemic rat heart catalyzed by distinct blood-borne and tissue factors. Am J Physiol Heart Circ Physiol 295: H2143-H2148, 2008. First published September 26, 2008 doi:10.1152/ajpheart.00050.2008.-Nitric oxide (NO) may limit myocardial ischemia-reperfusion injury by slowing the mitochondrial metabolism. We examined whether rat heart contains catalysts potentially capable of reducing nitrite to NO during an episode of regional myocardial ischemia produced by temporary coronary artery occlusion. In intact Sprague-Dawley rats, a 15-min coronary occlusion lowered the nitrite concentration of the myocardial regions exhibiting ischemic glucose metabolism to ϳ50% that of nonischemic regions (185 Ϯ 223 vs. 420 Ϯ 203 nmol/l). Nitrite was rapidly repleted during subsequent reperfusion. The heart tissue tested in vitro acquired a substantial ability to consume nitrite when made hypoxic at neutral pH, and this ability was slightly enhanced by simultaneously lowering the pH to 5.5. More than 70% of this activity could be abolished by flushing the coronary circulation with crystalloid to remove trapped erythrocytes. Correspondingly, erythrocytes demonstrated the ability to reduce exogenous nitrite to NO under hypoxic conditions in vitro. In erythrocyte-free heart tissue, the nitrite consumption increased fivefold when the pH was lowered to 5.5. Approximately 40% of this pH-sensitive increase in nitrite consumption could be blocked by the xanthine oxidoreductase inhibitor allopurinol, whereas lowering the PO 2 sufficiently to desaturate myoglobin accelerated it further. We conclude that rat heart contains several factors capable of catalyzing ischemic nitrite reduction; the most potent is contained within erythrocytes and activated by hypoxia, whereas the remainder includes xanthine oxidoreductase and other pH-sensitive factors endogenous to heart tissue, including deoxymyoglobin. myocardial ischemia; nitric oxide; erythrocyte; xanthine oxidoreductase NITRIC OXIDE (NO), generated locally within the heart, regulates a large number of normal physiological processes (11). NO is also produced within regions of the heart damaged by ischemia or infarction, and its physiological role in this context has been controversial. Under some conditions ischemic NO appears to contribute to pathological injury (3, 22, 26), whereas under others it appears to limit myocardial injury by delaying the onset of the mitochondrial calcium permeability transition (1,4,8,10,12,20,25). Given the evanescent nature of NO in living tissues, a cytoprotective action would presumably require the formation of NO locally within the ischemic heart. Identifying mechanisms capable of generating NO within the ischemic heart may be an important step toward the development of new therapies to limit myocardial ischemic injury.Under aerobic conditions, the primary source of cardiac NO is thought to be NO synthases (NOS) expressed by the coronary endothelium and other cells resident within the myocardium. The requirement of NOS for physiological p...

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