Insulin reverses impaired acetylcholine-induced dilatation of the rat basilar artery during diabetes mellitus

The goal of this study was to determine whether treatment of diabetic rats with insulin reverses impaired nitric oxide synthase-dependent reactivity of the basilar artery in vivo. We measured the diameter of the basilar artery in non-diabetic rats, diabetic (streptozotocin; 50-60 mg/kg i.p.) rats, and diabetic rats treated with insulin implants in response to acetylcholine and nitroglycerin before and following topical application of N-G-monomethyl-L-arginine (L-NMMA). Reactivity of the basilar artery was measured 2-3 months after injection of streptozotocin. We found that topical application of acetylcholine (1.0 and 10 muM) produced dose-related dilatation of the basilar artery in nan-diabetic rats, which was inhibited (>80%) by topical application of L-NMMA (10 muM). In diabetic rats, the magnitude of vasodilation produced by acetylcholine was significantly less than in non-diabetic rats. Further, topical application of L-NMMA did not affect dilatation of the basilar artery in diabetic rats: in response to acetylcholine. In insulin treated diabetic rats, dilatation of the basilar artery in response to acetylcholine was significantly greater than that observed in either non-diabetic or diabetic rats. In contrast, dilatation of the basilar artery in response to nitroglycerin was similar in insulin treated diabetic rats, non-diabetic rats and diabetic rats. Topical application of L-NMMA only partially inhibited dilatation of the basilar artery in response to acetylcholine in diabetic rats treated with insulin. Thus, the findings of this study suggest that impaired acetylcholine-induced dilatation of the basilar artery during diabetes mellitus can be restored by treatment with insulin. Further, it appears that the contribution of cellular pathways, in addition to nitric oxide synthase, may contribute to dilatation of the basilar artery in response to acetylcholine in rats treated with insulin. (C) 2001 Elsevier Science B.V. All rights reserved.