Impact of Type 2 Diabetes on Nitric Oxide and Adrenergic Modulation of Myocardial Perfusion

Abstract

Type 2 diabetic patients are characterized by a reduced adenosine-induced hyperemic myocardial perfusion, which may contribute to their increased cardiovascular morbidity. We hypothesized that the reduced hyperemia can be explained by functional changes in endothelial or autonomic nervous regulation. In 12 type 2 diabetic patients without signs of ischemic heart disease and 14 age-matched control subjects, myocardial perfusion was measured at rest, during adenosine, and during adenosine and ␣-receptor blockade (phentolamine) using positron emission tomography on two separate days: 1) with, and 2) without nitric oxide (NO) inhibition with N G -nitro-L-arginine methyl ester. Myocardial perfusion during adenosine was lower in type 2 diabetic patients compared with control subjects (P ‫؍‬ 0.05). No significant effect of NO inhibition on myocardial perfusion during adenosine was found in any of the groups. In control subjects, ␣-receptor blockade increased hyperemic myocardial vascular resistance during NO inhibition, whereas no effect was observed in type 2 diabetic patients. At rest, a significant correlation was observed between rate-pressure product and myocardial perfusion in control subjects. NO inhibition and type 2 diabetes abolished this correlation. Endothelial and cardiac autonomic nerve function seems to play only a minimal role in the reduced hyperemic myocardial perfusion in type 2 diabetic patients. However, the linear correlation between resting perfusion and cardiac work appears to be abolished in type 2 diabetes and during NO synthase inhibition. Diabetes 56: 468 -475, 2007

Endothelial Dysfunction in Recently Diagnosed Type 2 Diabetic Patients Evaluated by PET

“…Type 2 diabetes is characterized by reduced adenosine-induced hyperemic myocardial perfusion [24]. In our study, MBF during adenosine stress was significantly lower in the diabetic group compared to the HC control group.…”

“…A diminished MBF response to CPT is strongly associated with endothelial dysfunction [7,9,23]. Hyperglycemia in type 2 DM has been related to an increased production of reactive oxygen species, which results in inactivation of nitric oxide [24]. Nitric oxide is a key component of normal vascular tone [25].…”