No abstract

Previous investigations into the health effects of nitrogen oxides (NOJ) have mostly been conducted with special reference to nitrogen dioxide (NO2) and its direct effects on the respiratory system, while the study of nitric oxide (NO) has been disregarded. We carried out a study on NO by exposing rats and mice to 15NO or administering 15N-nitrite and 15N-nitrate to these animals by IP injection in order to elucidate the metabolic fate of NO.The results of our study and previous findings led us to assume that the major metabolic path of inhaled NO is as follows: inhaled NO reacts with hemoglobin, forming nitrosyl-hemoglobin (NOHb), and from NOHb, nitrite (NO-) and nitrate (NO-) are generated. Major quantities of NO-are discharged into the urine and a certain amount is discharged into the oral cavity through the salivary glands and transformed to NO-. Part of this NO is converted to N2 gas in the stomach. Nitrate in the intestine is partly reduced to ammonia (NH3) through NO-, reabsorbed into the body, and converted to urea. Most of the metabolites of inhaled NO are excreted rapidly from the body within 48 hr.

No abstract

Biotransformation of NO, nitrite and nitrate was investigated in rats and mice in a 15NO inhalation experiment and intraperitoneal injection experiments of 15N-nitrite and 15N-nitrate, and the following results were obtained: (1) Rats were forced to inhale 15NO (145 ppm, 123 minutes) or were given an intraperitoneal injection of 15N-nitrite (2 mg animal-1 as 15N) or 15N-nitrate (2mg animal-1 as 15N), and determination of 15N recovery in urine was made up to 48 h later. The results were 55, 53 and 78% of the inhaled or injected 15N, respectively. (2) 15N-nitrate in the urine was converted into a 6-nitro derivative of 3,4-xylenol and its identification and quantitative determination were made by the GC-MS method. As to 15N-urea in the urine, identification and quantitative determination were made by the urease method. 15N was present in the urine of rats after 15NO inhalation in the form of NO3- and urea. 75 and 24% respectively. In the urine of rats injected with 15N-nitrite, about 20% of unidentified 15N-compounds not discovered in the inhalation experiment was found. The content of 15N-urea in the urine after injection with 15N-nitrate was lower than that after injection with 15N-nitrite. (3) When 15N-nitrite (0.617 mg animal-1 as 15N) was injected intraperitoneally in mice, 60.7, 7.8 and 0.3% of the injected 15N were found in the urine, feces and exhaled gas (NO, NO2 and NH3 in the gas were caught) up to 48 h after injection respectively, and 1.6% was found in the body 48 h after injection, but the remaining 30% of 15N could not be recovered.

Previous investigations into the health effects of nitrogen oxides (NOx) have mostly been conducted with special reference to nitrogen dioxide (NO2) and its direct effects on the respiratory system, while the study of nitric oxide (NO) has been disregarded. We carried out a study on NO by exposing rats and mice to 15NO or administering 15N-nitrite and 15N-nitrate to these animals by IP injection in order to elucidate the metabolic fate of NO. The results of our study and previous findings led us to assume that the major metabolic path of inhaled NO is as follows: inhaled NO reacts with hemoglobin, forming nitrosyl-hemoglobin (NOHb), and from NOHb, nitrite (NO2-) and nitrate (NO3-) are generated. Major quantities of NO3- are discharged into the urine and a certain amount is discharged into the oral cavity through the salivary glands and transformed to NO2-. Part of this NO2- is converted to N2 gas in the stomach. Nitrate in the intestine is partly reduced to ammonia (NH3) through NO2-, reabsorbed into the body, and converted to urea. Most of the metabolites of inhaled NO are excreted rapidly from the body within 48 hr.