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

1 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-de pendent relaxation using aortic strips. 2 Aortae from diabetic rats, but not those from high-insulin-treated diabet ic rats, showed an impaired endothelium-dependent in response to acetylchol ine (ACh) by comparison with untreated controls. 3 Isotonic high K+-induced contractility was impaired in diabetic aortae. T his impairment was prevented by high-insulin treatment. 4 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. 5 In the combined presence of the nitric oxide inhibitor N-G-nitro-L-argini ne and the cyclooxygenase 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. 6 An increased expression of the mRNA for the alpha(1D) and alpha(1B) adren ergic receptors was found in aortae from high-insulin-treated diabetic rats . 7 These results demonstrate that in rats with established STZ-induced diabe tes, high-insulin treatment prevents the development of an impaired endothe lium-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 alpha(1B) or alpha(1D) adrenergic rec eptor that is secondary to the hyperinsulinaemia.