Molecular Mechanisms Of The Crosstalk Between Angiotensin II and Aldosterone

Abstract: The Crosstalk between aldosterone (Aldo) and angiotensin II (Ang II) is associated with vascular diseases such as inflammation, fibrosis and remodeling. The involved molecular mechanisms are unclear, but we hypothesized and tested the crosstalk to c-Src, ERK1/2 and NFAT specifically, considering the essential role of cholesterol rich domains (CRDs), and ROS generation. We evaluated the NFAT role on induced proliferation As well as Comprehension whether the crosstalk between Aldo and Ang II is exacerbated or different in VSMCs from SHRSP. Methods and Results: we studied VSMCs from WKY rats. At a low dose (10(- 10) mol/L) Aldo and Ang II did not stimulate c-Src or ERK1/2 phosphorylation individually, whereas the crosstalk increased phosphorylation for both in the presence of CRD (P<0.05) vs control. Also, the crosstalk induced synergistic effect on ROS production vs controls (P<0.05). At the same time, the effect of ROS on c-Src and ERK1/2 vs control is (P<0.05). This synergism increased Also phosphorylation of GSK3 β, thus activation of NFAT (P<0.05). The differences of cell signaling induced by crosstalk at this low concentration including Role of CRDs on ROS, c-Src, ERK1/2 and P38 is significant (P<0.05) between VSMCs from WKY and SHRSP. Conclusion: synergistically the crosstalk between Aldo/Ang II activates c-Src, and ERK1/2 involved the CRD, which may contain Noxs. This crosstalk also may regulate other cellular responses such as NFAT, which is involved in proliferation, cell hypertrophy and inflammation. These findings indicate differential signaling between VSMCs from WKY and SHRSP. Identification of these molecular mechanisms may be useful in the treatment of vascular diseases.