Methylglyoxal Impairs β₂-Adrenoceptor-Mediated Vasodilatory Mechanisms in Rat Retinal Arterioles

Methylglyoxal, a highly reactive dicarbonyl compound, is formed as a by-product of glycolysis and plays an important role in the pathogenesis of diabetic complications, including diabetic retinopathy. However, it remains to be determined how methylglyoxal affects the regulatory mechanisms of retinal blood flow. In this study, we examined the effects of methylglyoxal on β₂-adrenoceptor-mediated vasodilatory mechanisms in rat retinal arterioles. The retinal vasodilator responses were assessed by measuring the diameter of retinal arterioles in the fundus images. Intravitreal injection of methylglyoxal significantly diminished the vasodilation of retinal arterioles induced by the β₂-adrenoceptor agonist salbutamol. The vasodilator effect of BMS-191011, a large-conductance Ca²⁺-activated K⁺ (BK_Ca) channel opener, on retinal arterioles was also attenuated by methylglyoxal. In contrast, methylglyoxal had no significant effect on retinal vasodilator response to forskolin. Methylglyoxal attenuated retinal vasodilator response to salbutamol under blockade of BK_Ca channels with iberiotoxin, an inhibitor of the channels. These results suggest that methylglyoxal attenuates β₂-adrenoceptor-mediated retinal vasodilation by impairing the coupling of the β₂-adrenoceptor to the guanine nucleotide-binding protein (Gs protein) and the function of the BK_Ca channel. Increased methylglyoxal in the eyes may contribute to the impairment of regulatory mechanisms of retinal blood flow in patients with diabetic retinopathy.