The systemic effects of the combination of diabetes and hypercholesterolemia on venous vasomotor function are poorly understood. This study examines in vitro vasomotor responses of New Zealand White rabbit jugular veins from control, diabetic, hypercholesterolemic, and hypercholesterolemic with diabetes groups. Hypercholesterolemia was induced with a diet supplemented with 1% cholesterol, while diabetes was induced by alloxan. Cumulative dose response curves to norepinephrine, bradykinin, and histamine were performed. After precontraction with norepinephrine to give 80% maximal contraction, relaxation in response to acetylcholine and sodium nitroprusside was determined. Potency of the agonist responses were compared. The contractile responses to all agonists were significantly increased in hypercholesterolemia. Only 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 decreased, but the norepinephrine response was unchanged. There was dose-dependent, endothelium-mediated relaxation in precontracted control and diabetic veins. Hypercholesterolemia and hypercholesterolemia with diabetes interfered with endothelium-mediated relaxation, producing a multiphasic response: relaxation at low concentrations followed by contraction at higher concentrations. Non-endothelium-dependent relaxation to sodium nitroprusside of precontracted veins was unaffected by the presence of diabetes or hypercholesterolemia. This study suggests that the combined presence of diabetes and hypercholesterolemia attenuated the altered contractile responses induced by hypercholesterolemia alone without further alterations in endothelial-mediated responses. The mechanism for these alterations remains to be determined.
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