Effect of insulin treatment on smooth muscle contractility and endothelium-dependent relaxation in rat aortae from established STZ-induced diabetes

摘要

class="enumerated" style="list-style-type:decimal">This study involved the chronic administration of low or high insulin to rats with established streptozotocin (STZ)-induced diabetes. We studied the effect of such treatment on smooth muscle contractility and endothelium-dependent relaxation using aortic strips.Aortae from diabetic rats, but not those from high-insulin-treated diabetic rats, showed an impaired endothelium-dependent in response to acetylcholine (ACh) by comparison with untreated controls.Isotonic high K⁺-induced contractility was impaired in diabetic aortae. This impairment was prevented by high-insulin treatment.Noradrenaline (NA)-induced contractility was enhanced in aortae from high-insulin-treated diabetic rats, but not in those from untreated diabetic or low-insulin treated diabetic rats.In the combined presence of the nitric oxide inhibitor N^G-nitro-L-arginine and the cyclo-oxygenase inhibitor indomethacin, NA-induced contractility was significantly greater in aortae from high-insulin-treated diabetic rats than in those from controls or untreated diabetic rats.An increased expression of the mRNA for the α1D and α1B adrenergic receptors was found in aortae from high-insulin-treated diabetic rats.These results demonstrate that in rats with established STZ-induced diabetes, high-insulin treatment prevents the development of an impaired endothelium-dependent relaxation in the aorta, and that such treatment enhances NA-induced contractility. This enhancement may be related to an upregulation in the expression of the mRNA for the α1B or α1D adrenergic receptor that is secondary to the hyperinsulinaemia.