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This Article Full Text Full Text (PDF) All Versions of this Article: 93/8/954    most recent expphysiol.2007.041442v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Shahid, M. Articles by Fahim, M. PubMed PubMed Citation Articles by Shahid, M. Articles by Fahim, M. Related Collections Cardiovascular control

¹ Department of Physiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India ² Department of Pharmacology, University College of Medical Sciences and GTB Hospital, University of Delhi, Dilshad Garden, Delhi 110095, India

The present study was conducted to examine the role of nitric oxide (NO), mitochondrial ATP-sensitive K⁺ channels (mito K⁺_ATP channels) and reactive oxygen species (ROS) and their interdependence in brief femoral artery ischaemia-induced myocardial preconditioning. To assess myocardial injury, myocardial infarction was induced by occlusion followed by reperfusion of the left anterior descending (LAD) coronary artery in anaesthetized rats and was assessed by triphenyl tetrazolium chloride (TTC) staining. Left ventricular function was assessed by left ventricular end-diastolic pressure (LVEDP) and the maximal rate of rise of left ventricular pressure [LV(dP/dt)_max]. Serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) were determined by colorimetric kits. Remote preconditioning (RPC) was induced by 15 min occlusion of femoral arteries followed by 10 min of reperfusion just before LAD coronary artery occlusion. Brief femoral artery ischaemia led to a 61% reduction in myocardial infarct size, 57% reduction in elevated serum LDH and 72% reduction in elevated CK-MB activities, and a significant improvement in LVEDP and LV(dP/dt)_max compared with control animals. Pretreatment with 5-hydroxydecanoate (5-HD) or L-NAME or N-acetylcystein (NAC) blocked this protective effect of femoral artery ischaemia. Moreover, infusion of L-arginine or diazoxide before coronary artery occlusion markedly reduced the myocardial infarction and improved the left ventricular function. This effect of L-arginine was found to be abolished by the blockade of mito K⁺_ATP channels with 5-HD and, similarly, the effect of diazoxide was blocked in the presence of a ROS scavenger, NAC. The results suggest that brief femoral artery ischaemia-induced RPC is mediated by a combination of increased NO synthesis, opening of mito K⁺_ATP channels and increased ROS production. Moreover, it appears that NO is working upstream and acts via activation of mito K⁺_ATP channels, which subsequently increases the production of ROS.

(Received 15 November 2007; accepted after revision 19 March 2008; first published online 20 March 2008)
Corresponding author M. Fahim: Department of Physiology, Vallabhbhai Patel Chest Institute, University of Delhi, PO Box 2101, Delhi 110007, India. Email: vpciphysiology{at}yahoo.com