Objective: The balance between nitric oxide (NO)-sensitive and -insensitive forms of soluble guanylate cyclase (sGC) has been demonstrated to be disrupted in certain lifestyle-related diseases. However, it remains unclear whether type 2 diabetes results in a shift of sGC to the NO-insensitive form. This study addressed this issue in the human blood vessel.
Methods: Internal thoracic arteries were obtained from patients undergoing coronary artery bypass grafting. Helically cut strips of the arteries were suspended in organ chambers, and relaxant responses to nitroglycerin (NO-sensitive sGC stimulant) and BAY 60-2770 (NO-insensitive sGC stimulant) were assessed.
Results: The patients were divided into two groups according to the presence of type 2 diabetes (HbA1c: 7.0±0.3%) or its absence (HbA1c: 5.6±0.1%). Nitroglycerin-induced relaxation was not different in the arteries obtained from type 2 diabetic and non-diabetic patients. In addition, the relaxant response to BAY 60-2770 in type 2 diabetics was comparable to that observed in non-diabetics. Although the patients enrolled often had vascular risk factors other than type 2 diabetes, the relaxant responses were still in the same range in a comparison based on the number of risk factors. However, in separate experiments, the relaxant response to nitroglycerin was attenuated by pre-incubation of the arteries with ODQ (sGC imbalance inducer), whereas the relaxant response to BAY-60-2770 was augmented.
Conclusions: These findings suggest that type 2 diabetes does not affect the balance between NO-sensitive and -insensitive sGC in human internal thoracic artery grafts.
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