Nitric Oxide Solutions

Intravenous application of an NO-saturated saline solution exerts systemic hemodynamic effects, as judged by a significant dilation of resistance and conduit arteries in the contralateral arm and a transient and modest decrease in arterial blood pressure. The formation of RSNO and the dilatory response lasted several orders of magnitude longer than the previously suggested half-life of NO in vivo, thus ruling out that the transport of free NO contributes significantly to the sustained dilation seen in both conduit and resistance vessels. In support of the conclusion that plasma RSNOs are involved in the systemic vascular effects of intravenously applied aqueous NO solution, its hemodynamic response was mimicked by intravenous application of S-nitrosoglutathione [3].

In the future, systemic application of authentic NO may substitute NO deficiency as seen in various cardiovascular diseases associated with endothelial dysfunction. The route of administration and the chosen dose may critically determine NO transport and biological effects. This includes uptake, transport, and liberation of NO along the vascular tree by physiological blood-borne carriers, the intercellular contact of blood cells during passage through the microvasculature, and the interaction of plasmatic NO stores with the endothelium and vascular smooth muscle. The metabolism and distribution of NO and thus its range of action may exhibit significant spatial heterogeneity in vivo, depending on vessel size, hematocrit, flow velocity, and shear rates [64] as well as oxygen saturation and tissue pO2. These variables are expected to affect NO consumption in the RBC-free plasma zone near the vascular wall, and within RBCs [65,66]. Matters are further complicated by the fact that the RBC membrane represents a heterogenous sink [30,67], which may critically determine the effects of NO on the microcirculation [68]. These denominators might be affected differently by intraarterial, intravenous, or inhalative NO substitution therapy. Whether the application of aqueous NO solution may offer therapeutic advantages over existing NO-related therapies and furthermore be suitable to exert systemic biological effects in vivo remains to be investigated.

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