Vascular relaxation signaling pathway involves several mediators. One of the major relaxing factors is nitric oxide (NO). It is produced by the enzymes nitric oxide synthases (NOS). Among the NOS isoforms: NOS-1 (neuronal), NOS-2 (inducible) and NOS-3 (endothelial), the present study will focus on NOS-3 (eNOS) as a cellular target. The NOS-1 and NOS-3 are constitutive enzymes and they depend on the cytosolic calcium transient to be activated. Endothelial dysfunction occurs in several cardiovascular diseases such as hypertension. Endothelial dysfunction is a multifactorial process, but the increased production of oxygen reactive species (ROS) seems to play a major role in this process. ROS production in the endothelial cells, in the medial layer and adventitia, leads to the impaired NO signaling to the vasodilators that act in an endothelium-dependent or endothelium-independent way. In addition to eNOS, other important enzymes like fosfolipases (iPLA) are modulated by the Ca2+ transient. The calcium ionophore A-23187 increases [Ca2+]c in the endothelial cells. As previously shown by our research group, it reduces the [Ca+2]c in the rat vascular smooth muscle cells in the femoral artery. These data suggest that Ca2+ influx induced by A23187, in the endothelial cells, is involved in the activation of eNOS. Therefore, this study aims to investigate the cellular mechanisms of the vascular relaxation caused by the [Ca2+]c increased influx promoted by the Ca2+ ionophore in the endothelial cells of normotensive (2K) and renal hypertensive (2K-1C) rat aorta and to investigate the contribution of ROS for these effects. With this purpose, we will use the A23187 in the vascular reactivity studies in the isolated aortic rings as well the flow cytometry studies in isolated endothelial cells from the 2K and 2K-1C rat aorta in order to measure ROS.
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