Nitric Oxide Resistance Linked to Vascular and Myocardial Dysfunction in Insulin Resistant Obese Children: A Novel Aortic Strain Study.

Abstract

Background: Obesity impairs vascular compliance and myocardial functions; however, the intricate pathogenesis of this dysfunction is still elusive. There is conflicting evidence on serum nitric oxide (NOx) regulation in obesity, and some reports state that its bioavailability is reduced, while some others claim that it is upregulated. This study aimed to measure NOx status in obesity, to correlate it to vascular function, and to determine if myocardial function is tied to vascular dysfunction or not.

Patients and methods: For this purpose, 20 obese patients underwent serum NOx testing, serum testing of postprandial C-peptide to glucose ratio (PCPRI), vascular function testing using conventional flow-mediated dilation (FMD) of brachial artery, and the advanced aortic strain rate (ASR), in addition to myocardial functions using speckle tracking echocardiography. The latter in addition to serum NO was benchmarked against 16 healthy controls.

Results: Serum NOx was significantly higher in cases compared to controls (obesity group: 106 ± 14 vs. control group: 62 ± 9). The higher the insulin resistance (evidenced by high PCPRI), the higher was the NO level, denoting possibly a state of insulin-induced NO resistance. This NOx resistance was correlated with measures of vascular function, with ASR being more intimately related to serum NOx (r = 0.86 compared to an r = 0.66 with FMD). Lower ASR was tied to lower myocardial functions as expressed by global longitudinal strain, notably the subendocardial layer (r = 0.56 and r = 0.77, respectively).

Conclusion: Vascular dysfunction seen in obesity is probably orchestrated by a state of resistance to nitric oxide, induced by hyperinsulinemia. This vascular dysfunction seems to play a major role in reducing myocardial functions, especially the subendocardial component, which is known to be affected by impaired blood supply.