Half-life Of Nitric Oxide Research Articles

Effect of Inhaled Nitric Oxide on Cerebrospinal Fluid and Blood Nitrite Concentrations in Newborn Lambs

Inhaled nitric oxide (iNO) has many extrapulmonary effects. As the half-life of nitric oxide (NO) in blood is orders of magnitude less than the circulation time from lungs to the brain, the mediator of systemic effects of iNO is unknown. We hypothesized that concentrations of nitrite, a circulating byproduct of NO with demonstrated NO bioactivity, would increase in blood and cerebrospinal fluid (CSF) during iNO therapy. iNO (80 ppm) was given to six newborn lambs and results compared with six control lambs. Blood and CSF nitrite concentrations increased 2-fold in response to iNO. cGMP increased in blood but not CSF suggesting brain guanylate cyclase activity was not increased. When sodium nitrite was infused i.v. blood and CSF nitrite levels increased within 10 min and reached similar levels of 14.6 +/- 1.5 microM after 40 min. The reactivity of nitrite in Hb-free brain homogenates was investigated, with the findings that nitrite did not disappear nor did measurable amounts of s-nitroso, n-nitroso, or iron-nitrosyl-species appear. We conclude that although nitrite diffuses freely between blood and CSF, due to its lack of reactivity in the brain, nitrite's putative role as the mediator of the systemic effects of iNO is limited to intravascular reactions.

Half-life of nitric oxide in aqueous solutions with and without haemoglobin

Nitric oxide (NO) has been linked to many regulatory functions in mammalian cells. Studies of NO release are hampered by the short half-life of the molecule. In the blood, NO disappears within seconds because it binds avidly with haemoglobin (Hb). The relationship between Hb concentration and NO disappearance, however, has not been described. In this study we utilized an amperometric NO sensor (WPI, Sarasota, FL) to monitor continuously the disappearance of NO from an aqueous solution when Hb (free or as red blood cells) was added. The calibration and linearity of the NO sensor was checked frequently using a chemical reaction to generate a known concentration of NO. An aliquot of NO solution (prepared from authentic gas) was added to a glass beaker containing 20 ml saline to generate NO concentration of approximately 1200 nM. Under our experimental conditions , NO concentration fell slowly over 20 min with a half-life of 445 s. However, when haemoglobin was added, NO disappeared rapidly in proportion to Hb concentration. The results suggest that rapid binding of NO to Hb occurs in a 4:1 ratio. The maximum rate constant of NO disappearance due to binding with Hb was . The 4:1 binding ratio between NO:Hb may be used as a tool to quantitate NO release in some biological assays. The study supports the notion that NO acts as an autocoid because it disappears rapidly in the presence of Hb and is not likely to act as a circulating humoral substance. The NO sensor was useful for monitoring of NO concentration in Hb free solutions, but its response time limits its use in blood. Keywords: nitric oxide, haemoglobin, rate constant, temperature, meter

Manganese potentiation of nitric oxide-mediated vascular relaxation.

The half-life of nitric oxide (NO) and the relaxation of aortic-rings are enhanced by superoxide dismutase. Manganese and manganese-containing preparations have been reported to mimic superoxide dismutase activity. In the current study, manganese was tested for its ability to potentiate the activity of NO both in vitro and in vivo. Manganese relaxation of aortic segments was endothelium dependent as well as concentration dependent. Cyclic GMP concentrations in the segments were increased 2- and 4-fold with 5 and 300 microM manganese, respectively. N-Monomethyl-L-arginine pretreatment of aortic rings abolished the relaxation and cyclic GMP accumulation mediated by manganese. Infusion of manganese into conscious, restrained rats resulted in a decrease of blood pressure which was abolished by N-nitro-L-arginine pretreatment. Therefore, manganese may prolong the half-life of NO by a mechanism that mimics the action of superoxide dismutase resulting in potentiation of NO actions in vascular tissue.

Oxidation of nitric oxide by oxygen in biological systems monitored by porphyrinic sensor

A porphyrinic sensor was used to monitor the reaction of nitric oxide (NO) with oxygen. In the absence of biological material, the reaction rate is independent of the initial concentration of NO (zero order) and depends only on O 2 concentration (first order). At physiologic concentration of NO and O 2, the half-life of nitric oxide is in order of minutes and decreased to seconds only in the presence of biological material (intact cells).