A metabolic pathway of activated macrophages (M phi) involving oxidation of the guanido nitrogens of L-arginine is required for inhibition of growth and respiration of some target cells. The goal of this study was to identify the M phi metabolite(s) that induce these injuries. The stable products of the L-arginine pathway, NO2- and NO3-, were incapable of causing cytostasis under coculture conditions. However, NO2- became cytostatic upon mild acidification, which favors its transformation into nitrogen oxides of greater reactivity. This suggested that NO. (and/or NO2), recently identified as an M phi metabolite of L-arginine, could be a mediator. Authentic NO. caused cytostasis and respiratory inhibition in L1210 cells in a dose-dependent manner. The mitochondrial lesions caused by NO. were confined to complex 1 and 2, a pattern of injury identical to that seen after coculture with activated M phi. Inclusion of NO. scavenger systems prevented cytostasis from developing in M phi-L1210 cocultures. Thus, M phi-generated NO. can account for L-arginine-dependent cytostasis and respiratory inhibition.

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Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells

Background. The gas nitric oxide (NO) is an important endothelium-derived relaxing factor, inactivated by rapid combination with heme in hemoglobin. Methods and Results. Awake spontaneously breathing lambs inhaled 5-80 ppm NO with an acutely constricted pulmonary circulation due to either infusion of the stable thromboxane endoperoxide analogue U46619 or breathing a hypoxic gas mixture. Within 3 minutes after adding 40 ppm NO or more to inspired gas, pulmonary hypertension was reversed. Systemic vasodilation did not occur. Pulmonary hypertension resumed within 3-6 minutes of ceasing NO inhalation. During U46619 infusion pulmonary vasodilation was maintained up to 1 hour without tolerance. In the normal lamb, NO inhalation produced no hemodynamic changes. Breathing 80 ppm NO for 3 hours did not increase either methemoglobin or extravascular lung water levels nor modify lung histology compared with control lambs. Conclusions. Low dose inhaled NO (5-80 ppm) is a selective pulmonary vasodilator reversing both hypoxia- and thromboxane-induced pulmonary hypertension in the awake lamb [corrected].

Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.

Analysis of glutathione: implication in redox and detoxification.

This yearbook compiles the most recent developments in experimental and clinical research and practice in one comprehensive reference book. The chapters are written by well recognized experts in the field of intensive care and emergency medicine. It is addressed to everyone involved in internal medicine, anesthesia, surgery, pediatrics, intensive care and emergency medicine.

Yearbook of Intensive Care and Emergency Medicine

Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase

Studies on the function of abnormal hemoglobins I. An improved method for automatic measurement of the oxygen equilibrium curve of hemoglobin

Global allostery model of hemoglobin: Modulation of O2 affinity, cooperativity, and bohr effect by heterotropic allosteric effectors

Analyses of oxygen equilibria of native and chemically modified human adult hemoglobins on the basis of Adair's stepwise oxygenation theory and the allosteric model of Monod, Wyman, and Changeux.

Analysis of oxygen equilibrium of hemoglobin and control mechanism of organic phosphates.

Publisher Summary This chapter presents measurement of accurate oxygen equilibrium curves by an automatic oxygenation apparatus. The methods for measuring the oxygen equilibrium curve of hemoglobin are roughly separated into two groups: the static method and the dynamic method. In the static method, the curve is measured on a point-by-point base: it is obtained as a set of a finite number of points that are determined when the equilibrium between hemoglobin and oxygen has been established. The chapter discusses an automatic oxygenation apparatus and related techniques. This apparatus was originally designed to provide an easy and rapid means for studying the functional properties of increasing number of abnormal hemoglobins. The apparatus was further improved to measure more accurate equilibrium curves of more concentrated hemoglobin solutions. This improved method enables the measurement of equilibrium curves, which accurately allow the evaluation of the four oxygen equilibrium constants or the parameters of allosteric models by a least squares method.

Kiyohiro Imai

Papers

Studies on the function of abnormal hemoglobins I. An improved method for automatic measurement of the oxygen equilibrium curve of hemoglobin

Global allostery model of hemoglobin: Modulation of O2 affinity, cooperativity, and bohr effect by heterotropic allosteric effectors

Analyses of oxygen equilibria of native and chemically modified human adult hemoglobins on the basis of Adair's stepwise oxygenation theory and the allosteric model of Monod, Wyman, and Changeux.

Analysis of oxygen equilibrium of hemoglobin and control mechanism of organic phosphates.

[25] Measurement of accurate oxygen equilibrium curves by an automatic oxygenation apparatus