Angiotensin II and Angiotensin III Induce P38 Mitogen Activated Protein Kinase in Cultured Rat Astrocytes

Objective. In these studies, we determined whether angiotensin (Ang)II and Ang III induce p38 MAP kinase protein phosphorylation in rat astrocytes. Background. Previously we showed that these peptides induced phosphorylation of ERK1/2 and JNK mitogen activated protein (MAP) kinases in rat astrocytes. Methods. We used brainstem rat astrocytes as a model system to determine whether Ang II and Ang III induce p38 MAP kinase protein phosphorylation using western blotting techniques. Results. Treatment of astrocytes with increasing concentrations of both peptides caused a dose-dependent increase in p38 MAP kinase protein phosphorylation. The effects of Ang II and Ang III were maximal between 10 nM and 100 nM concentrations. The peptides effects were rapid and significant, occurring within minutes of treatment. Ang II\u27s ability to induce this kinase was significantly different (~2x as great) as compared to Ang III, suggesting that Ang II was more potent than Ang III in this effect. Ang AT1 receptor mediated the actions of the peptides since pretreatment with losartan prevented p38 MAP kinase phosphorylation by Ang II and Ang III. In addition, blockade of Ang II metabolism to Ang III with the aminopeptidase A inhibitor, glutamate phosphonate, was ineffective in ameliorating Ang II phosphorylation of p38 MAP kinase, suggesting that Ang II directly stimulated p38 MAP kinase phosphorylation. Conclusion. These findings provide insight into the molecular nature of the actions of these peptides and offer possible mechanisms by which these Ang peptides physiological and possibly pathological actions occur in astrocytes. Grants. Funded by PFRDG grant# 335465