Inactivation of myosin light chain phosphatase thorough myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation by Rho kinase is important for angiotensin II (Ang II)-induced constriction. However, the mechanism of Rho kinase activation by Ang II is unknown. We investigated whether Ang II-induced constriction in pressure-overloaded rat thoracic aortas is mediated by Rho kinase activation through Src, epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (Erk), and janus kinase (JAK).
The pressure-overload in rat thoracic aortas was produced by suprarenal abdominal aortic coarctation. After 4 weeks, thoracic aortas were excised and performed organ chamber experiments. Protein levels were measured by Western blotting.
Contractile response to Ang II significantly attenuated by inhibitors of Rho kinase, Erk1/2, Src, and EGFR in sham-treated and pressure-overloaded rats. Total and phosphorylated levels of MYPT1 and Src were increased in pressure-overloaded rat thoracic aortas. These data suggest that Ang II-induced constriction is mediated by Rho kinase activation via Src, EGFR, and Erk in pressure-overloaded rat thoracic aortas.