Abstrait

Oxygen kinetics, oxidative stress, and cardiac autonomic function in type 2 diabetes mellitus: Is nitric oxide the connecting link?

Shalini Verma

 

Type 2 diabetes mellitus (T2DM) is a multi-faceted metabolic disorder associated with a spectrum of complications, such as the commonly overlooked- cardiac autonomic neuropathy. Additionally, oxidative stress is increased in diabetes and may be linked to the development of chronic complications. T2DM is also shown to blunt the oxygen uptake kinetics, implying impairment of the control of oxygen delivery to and/or utilization of oxygen by contracting muscles. Nitric oxide (NO) has been proposed as a common denominator in the molecular mechanisms underlying these manifestations; however its behavior in diabetics is still controversial. Purpose: The purpose of this study was to examine the correlation between levels of nitric oxide and oxygen uptake kinetics, antioxidant defense, and autonomic function in patients with type 2 diabetes. Methods: Sixty T2DM patients were assessed for plasma levels of nitric oxide, oxygen uptake kinetics (time constant of steady state), antioxidant enzymes (catalase, superoxide dismutase), and cardiac autonomic function (heart rate variability). Results: Our results revealed that NO levels were correlated positively with τVO2 (r = 0.503), LFnu (r = 0.334), and LF: HF ratio (r = 0.270), and negatively with CAT (r = -0.456), AvgNN (r = -0.384), RMSSD (r = -0.323), and pRR50 (r = -0.353). Conclusion: Nitric oxide levels showed a negative correlation with antioxidant enzymes, oxygen uptake kinetics, and vagal indices of heart rate variability. These results are contradictory to the previously proposed protective effects of nitric oxide.

Nitric oxide (NO) may be a small radical with critical signaling roles in physiology and pathophysiology. The generation of sufficient NO levels to manage the resistance of the blood vessels and hence the upkeep of adequate blood flow is critical to the healthy performance of the vasculature. A novel paradigm indicates that classical NO synthesis by dedicated NO synthases is supplemented by nitrite reduction pathways under hypoxia. At an equivalent time, reactive oxygen species (ROS), which include superoxide and peroxide , are produced within the system for signaling purposes, as effectors of the immune reaction , or as byproducts of cellular metabolism. NO and ROS are often generated by distinct enzymes or by an equivalent enzyme through alternate reduction and oxidation processes. ?