The dual effects of leptin on aortic rings with and without endothelium isolated from streptozotocin-induced diabetic rats.

The aim of this study was to examine the effects of leptin on aortic rings with and without endothelium isolated from streptozotocin (STZ)-induced diabetic and control rats, and also in the presence of an inhibitor of nitric oxide synthase (NOS). Thoracic aortic rings from 5-week STZ-induced diabetic (50 mg/kg i.p.) and age-matched control Sprague-Dawley rats were mounted in isolated tissue baths. Concentration-response curves to leptin (0.1 pM-1 nM) were constructed under basal tone and after precontraction with 1 microM phenylephrine in the presence or absence of Nomega-nitro-L-arginine methyl ester (L-NAME, 10 microM). Leptin caused a concentration-dependent relaxation of precontracted endothelium-intact aortic rings from control and diabetic rats. Responses to leptin in diabetic aorta were significantly increased compared to those of controls (P < 0.05). EC(50) values for leptin were similar for aortic rings from diabetic and control rats (P > 0.05). L-NAME pretreatment caused complete inhibition of the relaxant responses to leptin in the control aortic rings, while it induced a reduction in these responses in the diabetic rings (P < 0.05). Leptin-induced relaxation was eliminated when the endothelium was denuded. Leptin had no effect on the basal tone of endothelium-intact or -denuded aortic rings from control rats. In diabetic rings, leptin elicited concentration-dependent contractions (P < 0.05). Removal of the endothelium significantly increased the contractile effect of leptin on basal tone in diabetic rings (P < 0.05). The results suggest that leptin may induce vasodilatation by endothelial mechanism(s) other than nitric oxide (NO) release from the endothelium in diabetic aortic rings. On the other hand, leptin causes contractile effects on the basal tone in aorta smooth muscle isolated from STZ-induced diabetic rats. The contractile effect of leptin on basal tone may contribute to the development of hypertension in diabetes.