In-vivo nitric oxide synthesis is reduced in obese patients with metabolic syndrome: application of a novel stable isotopic method

Objectives Nitric oxide synthesis is declined in cardiovascular and metabolic diseases associated with endothelial dysfunction such as type 2 diabetes, hypertension or congestive heart failure. The objectives were to validate a novel stable isotopic method for the determination of in-vivo nitric oxide synthesis and to evaluate differences in nitric oxide synthesis in obese patients with and without metabolic syndrome (MetSyn). Methods The new method, called oral nitrate test (ONT), measured the decay in saliva or urine samples of an oral dose of labelled sodium nitrate. The ONT method was compared to a validated method (frequent sampling arginine test, FSAT method) in 10 healthy adult volunteers (BMI range=20.8-27.3 kg/m(2)). The accuracy of the saliva ONT method was then tested by measuring nitric oxide synthesis in seven healthy, normal weight individuals, seven obese patients without MetSyn and seven obese patients with MetSyn. Results The estimated rate of nitric oxide synthesis was 0.63+/-0.20 mu mol/h per kg from the data obtained from saliva, and 0.50+/-0.14 mu mol/h per kg from urine. The agreement of the saliva ONT method with the FSAT method (Delta=+0.02+/-0.24; P=0.79) was superior to the urine ONT method (Delta=-0.11+/-0.20; P=0.13). Obese patients with MetSyn had a significantly lower nitric oxide production rate (0.21+/-0.13 mu mol/h per kg; P=0.009) than healthy normal weight individuals (0.63+/-0.30 mu mol/h per kg), whereas nitric oxide production rate was intermediate in obese patients without MetSyn (0.49+/-0.22 mu mol/h per kg; P=0.33). Conclusion The advantages of the new saliva ONT method are its accuracy, sensitivity and lack of invasiveness, which could make it a reference method for the assessment of in-vivo rates of whole-body nitric oxide synthesis. J Hypertens 29: 1515-1527 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.