What Is the Reason that Gaseous Nitric Oxide Inhalation Does Not Affect Systemic Arterial Pressure in Humans and Animals?

Abstract

The reason for the lack of the hypotensive effect of gaseous NO, as introduced by inhalation into the bodies of animals and humans, has been identified. Since this defect was completely eliminated by inhalation of NO simultaneous with intravenous administration of low molecular mass thiol solutions to animals (rats), it is concluded that gaseous NO entering through the lungs into the blood circulating in a large circle of blood circulation converts into nitrosonium cation (NO⁺) as a result of single-electron oxidation, which is unable to exert vasodilating and thereby hypotensive effects on animals and humans. The binding of NO⁺ to low molecular mass thiols leads to its transformation into S-nitrosothiols, followed by the release of this nitrosyl agent in the form of neutral NO molecules characterized by hypotensive activity. The formation of dinitrosyl iron complexes with thiol-containing ligands in the blood and tissues of organs of experimental animals in these experiments, which could cause a hypotensive effect, was not detected. The hypotensive effect of inhaled NO, which was found in the lungs, could be due to the penetration of NO through the outer wall of blood vessels with subsequent activation of the enzyme guanylate cyclase, an inducer of vasodilation and hypotension, directly in the walls of blood vessels.