Evidence for in vivo transport of bioactive nitric oxide in human plasma

Abstract

Although hitherto considered as a strictly locally acting vasodilator, results from recent clinical studies with inhaled nitric oxide (NO) indicate that NO can exert effects beyond the pulmonary circulation. We therefore sought to investigate potential remote vascular effects of intra-arterially applied aqueous NO solution and to identify the mechanisms involved. On bolus application of NO into the brachial artery of 32 healthy volunteers, both diameter of the downstream radial artery and forearm blood flow increased in a dose-dependent manner. Maximum dilator responses were comparable to those after stimulation of endogenous NO formation with acetylcholine and bradykinin. Response kinetics and pattern of NO decomposition suggested that despite the presence of hemoglobin-containing erythrocytes, a significant portion of NO was transported in its unbound form. Infusion of NO (36 µmol/min) into the brachial artery increased levels of plasma nitroso species, nitrite, and nitrate in the draining antecubital vein (by < 2-fold, 30-fold, and 4-fold, respectively), indicative of oxidative and nitrosative chemistry. Infused N-oxides were inactive as vasodilators whereas S-nitrosoglutathione dilated conduit and resistance arteries. Our results suggest that NO can be transported in bioactive form for significant distances along the vascular bed. Both free NO and plasma nitroso species contribute to the dilation of the downstream vasculature.

Beetroot juice improves in overweight and slightly obese men postprandial endothelial function after consumption of a mixed meal

“…Both test meals (Supplemental Table 1 to as the circulating NO pool (NOx), were determined using a triiodide/ozone-based chemiluminescence assay as described (11). RXNO and nitrite analyses were carried out in lithium heparin plasma samples collected at T0, 60, 120 and 240.…”

Plasma detection of NO by a catheter

“…However, growing experimental and clinical evidence suggests that NO remain active in blood stream, causing remote biological response [45,71]. Accordingly, measurement of plasma NO concentration directly in the circulation will contribute to clarify the kinetics and physiological roles of NO and to evaluate endothelial function.…”

Abnormal metabolic fate of nitric oxide in Type I diabetes mellitus

“…It has recently been shown [26] that an infusion of 36 µmol/min nitric oxide or 5 nmol/min S-nitrosoglutathione into the brachial artery of healthy subjects resulted in large increases in downstream radial artery diameter and forearm blood flow that were comparable to those after stimulation of endogenous nitric oxide formation with acetylcholine or bradykinin. These results provide evidence that this concentration of transported nitric oxide is bioactive in human blood and the increased concentrations reported in our study represent a physiologically significant pool of nitric oxide.…”