Diabetes is a major risk factor for vascular diseases, and often associated with vascular dysfunction. However, the mechanisms of vascular dysfunction in diabetes are not fully understood. Inactivation of myosin light chain phosphatase thorough myosin phosphatase targeting subunit 1 phosphorylation by Rho kinase is important for angiotensin II (Ang II)-induced contraction. We have previously reported that Rho kinase activation by Src, epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase 1 and 2 (Erk1/2) is involved in protein tyrosine phosphatase inhibitor-induced contraction. We therefore investigated the effects of inhibitors of these factors on Ang II-induced contraction in diabetic rat superior mesenteric arteries.
Wistar male rats were induced diabetes by intraperitoneal injection of streptozotocin (40 mg/kg). After 8 weeks, superior mesenteric arteries were excised and performed organ chamber experiments. Protein levels were measured by Western blotting.
The contraction of superior mesenteric arteries from diabetic rats increased in the response to Ang II in comparison with those from the control rats. However, we did not observe any differences in Ang II-induced contraction between the groups in the presence of Rho kinase, EGFR, and Erk1/2 inhibitors. Moreover, protein level of Erk1/2 was significantly increased in diabetic rats. These data suggest that increased activity of Rho kinase, EGFR, and Erk1/2 might be involved in excessive contraction by Ang II in superior mesenteric arteries of diabetic rats.