Attenuated alpha-adrenoceptor-mediated arterial and venous constrictions in rat models of diabetes

Diabetes is associated with metabolic and vascular abnormalities. We investigated if arterial and venous constrictions are impaired in rat models of diabetes. Wistar rats (5 weeks old) were fed a normal or high-fructose diet (60% of caloric intake). On Day 14, half of the animals in each diet regimen were given streptozotocin (60 mg/kg, i.v.). On Day 35, plasma insulin and triglyceride were measured, and on Day 42, insulin sensitivity (via hyperinsulinemic euglycemic clamp), and pressor as well as mean circulatory filling pressure (index of venous tone) responses to noradrenaline were determined. The rats treated with streptozotocin or fructose-streptozotocin were hyperglycemic, hypoinsulinemic and insulin resistant, and they also had reduced potency (increased ED(50)) of pressor response and reduced venoconstriction to noradrenaline compared to the two groups not given streptozotocin. Plasma triglyceride was unchanged in streptozotocin-treated rats, moderately increased in fructose-fed rats, and markedly increased in fructose-streptozotocin-treated rats. Hyperglycemia, insulin resistance and alpha-adrenoceptor-mediated venous contractile dysfunction were more pronounced in the group given fructose-streptozotocin than that given streptozotocin alone. The presence of marked hypertriglyceridemia, insulin resistance and vascular dysfunction makes the fructose-streptozotocin-treated rats a suitable model for study of metabolic and vascular abnormalities in advanced type 2 diabetes.