Diabetes attenuates the alterations in both venous endothelial and smooth muscle cell function induced by prolonged hypercholesterolemia in an experimental model

The systemic effects of the combination of diabetes and hypercholesterolemi a on venous vasomotor function are poorly understood. This study examines i n vitro vasomotor responses of New Zealand White rabbit jugular veins from control, diabetic, hypercholesterolemic, and hypercholesterolemic with diab etes groups. Hypercholesterolemia was induced with a diet supplemented with 1% cholesterol, while diabetes was induced by alloxan. Cumulative dose res ponse curves to norepinephrine, bradykinin, and histamine were performed. A fter precontraction with norepinephrine to give 80% maximal contraction, re laxation in response to acetylcholine and sodium nitroprusside was determin ed. Potency of the agonist responses were compared. The contractile respons es to all agonists were significantly increased in hypercholesterolemia. On ly the response to norepinephrine was increased in diabetes. However, when diabetes and hypercholesterolemia were combined the contractile response to bradykinin was increased, the response to histamine was significantly decr eased, but the norepinephrine response was unchanged. There was dose-depend ent, endothelium-mediated relaxation in precontracted control and diabetic veins. Hypercholesterolemia and hypercholesterolemia with diabetes interfer ed with endothelium-mediated relaxation, producing a multiphasic response: relaxation at low concentrations followed by contraction at higher concentr ations. Non-endothelium-dependent relaxation to sodium nitroprusside of pre contracted veins was unaffected by the presence of diabetes or hypercholest erolemia. This study suggests that the combined presence of diabetes and hy percholesterolemia attenuated the altered contractile responses induced by hypercholesterolemia alone without further alterations in endothelial-media ted responses. The mechanism for these alterations remains to be determined .