OBJECTIVE: Impaired endothelium-independent vasodilation is a known consequence of types 1 and 2 diabetes, and the mechanism of impaired vasodilation is not well understood. The following study investigated the effects of types 1 and 2 diabetes in endothelial-independent vasodilation associated with coronary vascular smooth muscle (VSM) relaxation and contractile signaling mechanisms. MATERIALS AND METHODS: Type 1 diabetes was induced in Yucatan miniswine via alloxan injection and treated with or without insulin (DM and IDM). Nondiabetic swine served as controls (ND). Expression and/or phosphorylation of determinants of VSM relaxation and contraction signaling were examined in coronary arteries and microvessels. Coronary microvessel relaxation was assessed by using sodium nitroprusside (SNP). In addition, SNP-induced vasodilation and myosin light-chain (MLC) phosphorylation was determined in coronary microvessels isolated from ND and type 2 diabetic human atrial appendage. RESULTS: Diabetic impairment in SNP-induced relaxation was completely normalized by insulin. Soluble guanylate cyclase (sGC) VSM expression decreased in both DM and IDM groups and did not correlate with vasorelaxation. Phosphorylation of MLC and myosin phosphatase increased in the DM group and MLC phosphorylation strongly correlated with impaired VSM relaxation (r=0.670, P<0.01). Coronary microvessels from type 2 diabetic human patients exhibited similarly impaired vasodilation and enhanced VSM MLC phosphorylation. CONCLUSIONS: Impaired vasodilation in type 1 diabetes correlates with enhanced VSM MLC phosphorylation. In addition, enhanced VSM MLC phosphorylation is associated with impaired vasodilation in type 2 diabetes in humans.
OBJECTIVE: Impaired endothelium-independent vasodilation is a known consequence of types 1 and 2 diabetes, and the mechanism of impaired vasodilation is not well understood. The following study investigated the effects of types 1 and 2 diabetes in endothelial-independent vasodilation associated with coronary vascular smooth muscle (VSM) relaxation and contractile signaling mechanisms. MATERIALS AND METHODS: Type 1 diabetes was induced in Yucatan miniswine via alloxan injection and treated with or without insulin (DM and IDM). Nondiabetic swine served as controls (ND). Expression and/or phosphorylation of determinants of VSM relaxation and contraction signaling were examined in coronary arteries and microvessels. Coronary microvessel relaxation was assessed by using sodium nitroprusside (SNP). In addition, SNP-induced vasodilation and myosin light-chain (MLC) phosphorylation was determined in coronary microvessels isolated from ND and type 2 diabetichuman atrial appendage. RESULTS:Diabetic impairment in SNP-induced relaxation was completely normalized by insulin. Soluble guanylate cyclase (sGC) VSM expression decreased in both DM and IDM groups and did not correlate with vasorelaxation. Phosphorylation of MLC and myosin phosphatase increased in the DM group and MLC phosphorylation strongly correlated with impaired VSM relaxation (r=0.670, P<0.01). Coronary microvessels from type 2 diabetichumanpatients exhibited similarly impaired vasodilation and enhanced VSM MLC phosphorylation. CONCLUSIONS: Impaired vasodilation in type 1 diabetes correlates with enhanced VSM MLC phosphorylation. In addition, enhanced VSM MLC phosphorylation is associated with impaired vasodilation in type 2 diabetes in humans.
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