SS19. Differential Expression of ERK and Akt Following Nitric Oxide Exposure in Type 1 and Type 2 Diabetic Rats

Diabetic patients develop greater restenosis from neointimal hyperplasia after vascular interventions. Previously, we reported that nitric oxide (NO) decreased neointimal hyperplasia significantly more in type 2 diabetic rats than controls, but not at all in type 1 diabetic rats. Given the different insulin levels between these animal models, and that insulin is known to regulate ERK and Akt, we hypothesized that NO differentially effects ERK and Akt activity in type 1 vs type 2 diabetic rats. To induce type 2 diabetes, Zucker diabetic fatty (ZDF) rats were fed Purina 5008 chow. To induce type 1 diabetes, lean Zucker (LZ) rats were injected with streptozotocin (STZ; 60mg/kg). Rats with glucose>300mg/dL were included in the study. Non-STZ LZ rats served as controls. The carotid artery injury model was performed. Groups included injury and injury+PROLI/NO (20 mg) [n = 6/group]. At 14 days, phosphorylated ERK (pERK) and Akt (pAkt) expression was assessed by immunofluorescent staining. There were no changes in pERK expression after NO treatment in LZ control and type 1 diabetic rats but increased expression in type 2 diabetic rats (44%, p < 0.009). This increase was observed mainly in the adventitia. pAkt expression decreased in the LZ control (47%, p < 0.012) and type 1 diabetic (51%, p < 0.043) rats after NO treatment but increased in type 2 diabetic rats (53%, p < 0.003). These changes occurred mostly in the neointimal and adventitia. Interestingly, NO increased the pERK/pAkt ratio by 29% in the LZ control and 47% in the type 1 diabetic rats but decreased the pERK/pAKT ratio by 12% in the type 2 diabetic rats. NO differentially effects the expression of pERK and pAkt in type 1 vs type 2 diabetic rats, by decreasing the pERK/pAkt ratio in type 2 diabetic but increasing this ratio in type 1 diabetic and control rats. These data suggest one mechanism by which NO inhibits neointimal hyperplasia in hyperinsulinemic environments.