Background We investigated the effects of cardiopulmonary bypass (CPB) on peripheral arteriolar reactivity and associated signaling pathways in poorly controlled (UDM), controlled (CDM), and case-matched non-diabetic (ND) patients undergoing coronary artery bypass grafting. Methods and Results Skeletal muscle arterioles were harvested pre- and post-CPB from the UDM patients (hemoglobin A1c [HbA1c] = 9.0 ± 0.3), the CDM patients (HbA1c = 6.3 ± 0.15) and the ND patients (HbA1c = 5.2 ± 0.1) undergoing CABG surgery (n = 10/group). In vitro relaxation responses of pre-contracted arterioles to endothelium-dependent vasodilators adenosine 5’-diphosphate (ADP) and substance P and the endothelium-independent vasodilator sodium nitroprusside (SNP) were examined. The baseline responses to ADP, substance P and SNP of arterioles from the UDM patients were decreased as compared to microvessels from the ND or CDM patients (P <0.05). The post-CPB relaxation responses to ADP and substance P were significantly decreased in all three groups compared to pre-CPB responses (P <0.05). However, these decreases were more pronounced in the UDM group (P <0.05). The post-CPB response to SNP was significantly decreased only in the UDM group, not in the other two groups compared to pre-CPB. The expression of PKC-α, PKC-β, protein oxidation and nitrotyrosine in the skeletal muscle were significantly increased in the UDM group as compared with those of ND or CDM groups (P<0.05). Conclusion Poorly controlled diabetes results in impaired arteriolar function before and after CPB. These alterations are associated with the increased expression/activation of PKC-α and PKC-β, and enhanced oxidative and nitrosative stress.

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