The event of ischemia followed by reperfusion (I/R) promotes injury to the cardiac tissue. I/R are major contributors to cardiac dysfunction and infarct size, and determine patient prognosis after acute myocardial infarction. However, attenuation of the lesions provoked by I/R are achieved by ischemic pre-conditioning (IPC). IPC is defined as a process in which the heart can be protected from an acute lethal I/R injury by applying non-lethal episodes of I/R either to the heart itself or to a distant organ or tissue.In addition, it has been suggested that nitric oxide (NO) and reactive nitrogen species produce a cytoprotection mimicking the action of preconditioning tolerance*.Recently, we described in bradykinin-stimulated endothelial cells a pro-angiogenic and pro-survival signaling pathway. NO synthase (NOS)-derived NO, the epidermal growth factor receptor (EGF-R) and the MAP Kinases ERK1/2 are essential components of this signaling pathway*. In the present communication we sought to determine in 6 month old male Wistar rats submitted to a predefined experimental protocol, whether NO, EGF-R and the ERK1/2 MAP kinases play a role in IPC applied to the mesenteric artery which irrigates the small intestine. Intestine and heart tissues were obtained from sham animals without any treatment, from animals that underwent IPC (5 min ischemia followed by 10 min reperfusion), and from animals submitted to 60 min of ischemia. We then performed histological and western blot analysis of the intestine and heart tissues from the experimental groups. Morphological changes of hematoxylin and eosin stained paraffin sections of the intestine were examined under light microscope. Structures were well preserved in the IPC group, whereas in the ischemia group they were not preserved.Western blot analysis revealed that the expression levels of the EGF-R were elevated in the heart of animals from the IPC group. Expression levels of inducible NOS were elevated in the heart and in the intestine of IPC animals. Expression of phosphorylated ERK1/2 MAP kinases was increased in the intestine of the animals from the IPC group. In conclusion, our data suggest a differential participation of the iNOS, the ERK1/2 MAP kinases, and the EGF-R in the signaling events occurring in heart and intestine tissues from animals submitted to IPC and ischemia compared to animals submitted to ischemia.