Enhanced hemodynamic response to [D-ALA2,D-MET5]-methionine enkephalin (DAME) in streptozotocin-induced diabetic rats is reversed by insulin replacement.

The present study examined the alterations of hemodynamic responses to [D-ala2,D-Met5]-methionine enkephalin (DAME) in diabetic animals. Male Sprague-Dawley rats (12 weeks old) were used for this study. Diabetes was induced by a single injection of streptozotocin (65 mg/kg, i.v.). After 7 days, blood glucose levels were determined to confirm the diabetic state. Animals were anesthetized and instrumented to monitor mean arterial pressure, hindlimb bloodflow and hindlimb vascular resistance. Administration of DAME produced a significantly greater reduction in blood pressure, increase in hindlimb bloodflow and decrease in hindlimb vascular resistance in diabetic vs. control rats. These effects were blocked by naloxone. All hemodynamic changes were attenuated after pretreatment with the ganglionic blocker, hexamethonium, indicating that the responses were mediated either within the central nervous system or at the ganglia. Insulin reversed the exaggerated depressor effect of DAME on streptozotocin-treated rats. Collectively, these results suggest that diabetic rats have altered opioidergic hemodynamic responses to DAME due to mu receptor alterations in the CNS or in autonomic ganglia. These effects were reversed by replacement of insulin.