Responses of cerebral arterioles to activation of beta-adrenergic receptors during diabetes mellitus.

Abstract

Diabetes mellitus impairs reactivity of large peripheral arteries and arterioles to activation of beta-adrenergic receptors. The goal of this study was to determine whether diabetes mellitus alters dilatation of cerebral arterioles to activation of beta-adrenergic receptors. In vivo diameter of pial arterioles was measured in nondiabetic and diabetic (streptozotocin 50 to 60 mg/kg IP) rats during superfusion with isoproterenol, forskolin, and nitroglycerin. In addition, we examined the contribution of nitric oxide or a nitric oxide-containing compound in dilatation of pial arterioles in response to the agonists. Dilatation of pial arterioles in response to isoproterenol was significantly less in diabetic compared with nondiabetic rats (3 +/- 2% versus 14 +/- 1%, respectively, for 1.0 mumol/L isoproterenol). In contrast, dilatation of pial arterioles in response to nitroglycerin and forskolin was similar in nondiabetic and diabetic rats. Furthermore, dilatation of pial arterioles in nondiabetic rats in response to isoproterenol and forskolin was not related to the synthesis and release of nitric oxide or a nitric oxide-containing compound. The findings of the present studies suggest that diabetes mellitus impairs dilatation of cerebral resistance arterioles in response to activation of beta-adrenergic receptors. Impairment of beta-adrenergic-mediated dilatation of cerebral arterioles during diabetes mellitus does not appear to be related to an alteration in cyclic adenosine monophosphate, since forskolin produced similar vasodilatation in nondiabetic and diabetic rats.