Abstract
Proliferation of vascular smooth muscle cells (VSMCs) and inflammation are well known actions associated with hypertension. Angiotensin (Ang) II mediates these physiological actions through the c-Jun N terminal Kinase (JNK), mitogen-activated proteins kinase (MAPK) pathway. Ang III effects on this pathway in VSMCs are unknown. The aim of this study was to determine whether Ang III activates JNK MAPK in Wistar VSMCs and determined whether the response was different in spontaneously hypertensive rat (SHR) VSMCs. We also ascertained whether this effect leads to VSMC proliferation. Western blots were used to determine the time and concentration effects of Ang II on JNK MAPK phosphorylation in Wistar VSMCs. Similar studies were conducted for Ang III in Wistar and SHR VSMCs. Both peptides induced JNK phosphorylation in a concentration- and time-dependent manner in Wistar VSMCs. Ang III also increased JNK phosphorylation in a concentration- and time-dependent fashion in SHR VSMCs as well. However, the ability of Ang III to induce JNK MAPK was different in SHR VSMCs as the phosphorylation levels of JNK were significantly higher in Wistar VSMCs as compared to SHR VSMCs at several time points and concentrations. Further, Ang III-mediated DNA synthesis, a measure of VSMC proliferation, occurred through activation of JNK MAPK. This study is the first to show Ang III effects on the JNK MAPK pathway in VSMCs and the role of JNK in Ang III-mediated cellular proliferation. These findings impart key information for the understanding of Ang III functions, especially in VSMCs and possible cardiovascular diseases.