Role of Angiotensin III on ERK1/2 and P38 Mitogen Activated Protein (MAP) Kinases in Wistar Rat VSMCs

Objective. We investigated whether angiotensin (Ang) III induces ERK1/2 and p38 mitogen activated protein (MAP) kinases protein phosphorylation in isolated rat vascular smooth muscle cells (VSMCs). Background. The molecular mechanisms by which Ang III induces various biological effects have not been fully investigated. Most studies have shown that MAP kinases mediate Ang II apoptosis and growth promoting effects in VSMCs. Moreover, Ang II induces vascular remodeling in these cells leading to increases in blood pressure. MAP kinases regulate or induce two crucial actions in VSMCs, proliferation and migration, which are associated with atherosclerosis and restenosis. Methods. Primary cultures of VSMCs were isolated from the thoracic aorta of adult Wistar rats by the explant technique. VSMCs were treated with Ang III ranging in concentration from 0.1 nM to 1000 nM for 10 minutes or with 100 nM Ang III for 1 minute to 30 minutes. Western blotting technique was used to determine whether Ang III induces ERK1/2 and p38 MAP kinases protein phosphorylation. Results. Concentration studies showed that Ang III caused a dose-dependent increase in ERK1/2 and p38 MAP kinases protein phosphorylation. The effects of Ang III on both MAP kinases phosphorylation were maximal between 10 nM and 100 nM concentrations. The peptide effects were rapid and significant, occurring within minutes of treatment and the maximal effects on MAP kinases phosphorylation was observed by 10 min. Conclusion. These findings provide insight into the molecular nature of the actions of Ang III and offer possible mechanism by which Ang III physiological and possibly pathological actions occur in VSMCs. Grants. Funding for this project was provided through a Nova Southeastern University Health Professions Division Grant and Saudi Arabian Cultural Mission