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Disturbed nitric oxide (NO) synthesis leads to development of endothelial dysfunction that plays a significant role in the pathogenesis of arterial hypertension. The presence of various compounds of haemoglobin with NO can affect haemoglobin-oxygen affinity of the whole blood. Methaemoglobin and S-nitrosohaemoglobin increase it, whereas nitrosyl-haemoglobin decreases. The aim of this study was to investigate the blood oxygen transport indices and to assess the endothelial function in patients with arterial hypertension. The patients with mild hypertension had a 4.47% increased actual p50 (the blood pO(2) corresponding to its 50% oxygen saturation) (P<0.05), a diminished pO(2) (P<0.05), and a raised pCO(2) (P<0.01) as compared with the controls. The patients with severe hypertension had decreased pO(2) and pH, and actual p50 was reduced by 3.03% (P<0.05), which reflects a more pronounced oxyhaemoglobin dissociation curve shift leftwards. These changes can be assessed as a blood oxygen transport decompensation that enhanced tissue hypoxia. The results of our studies indicate that the endothelial dysfunction in patients with arterial hypertension leads to significant impairments in blood oxygen transport indices. The endothelium may be involved in development of the above blood oxygen transport impairments, since only sufficient amounts of NO maintain a normal blood flow and oxygen transport to tissues. The endothelial dysfunction leads to a disturbed production of different haemoglobin NO derivatives, which not only affects NO release at different sites of the arterial bed, but also haemoglobin-oxygen affinity and optimal blood oxygenation and deoxygenation in capillaries. These data support the notion that endothelial dysfunction may alter haemoglobin-oxygen affinity and tissue oxygen supply in vivo. Alternation of haemoglobin-oxygen supply may be involved in the pathogenesis of hypertension.

Endothelial dysfunction, which is characterized by impairment of nitric oxide (NO) bioavailability, plays an important role in the development of arterial hypertension. The L-arginine-NO pathway is closely related to oxygen transport to tissue. Endothelial dysfunction in patients with arterial hypertension can affect haemoglobin-oxygen affinity and tissue oxygen supply. Alterations in blood oxygen transport indices may play role in the pathogenesis of arterial hypertension. The aim of the present study was to investigate the effect of the beta-selective adrenoblocker nebilet (nebivolol) on blood oxygen transport indices and on endothelial dysfunction in patients with arterial hypertension. The study population included 52 patients with grade II and grade III arterial hypertension. The results of our studies indicate that endothelial dysfunction in hypertensive patients significantly changes blood oxygen indices. The endothelium can be involved in formation of these impairments because only NO synthesized in sufficient amounts can maintain normal blood flow and oxygen transport to tissues. Endothelial dysfunction impairs formation of different haemoglobin NO-derivatives, that influence not only on the release of NO at different sites of the vascular bed, but also on haemoglobin-oxygen affinity, and accordingly, on optimal blood oxygenation in capillaries of pulmonary circulation and its deoxygenation in capillaries of systemic circulation. Treatment of hypertensive patients with nebivolol corrects the blood oxygen transport indices, stimulates NO production and improves endothelium-dependent dilatation. Normalization of blood oxygen transport indices may regulate the activity of the L-arginine-NO pathway. Thus, nebivolol may improve efficiency of the treatment of hypertension.

The aim of the present work was to evaluate oxidative stress in the brains of rats during ischemia/reperfusion in conditions of correction of the L-arginine-NO system. Experiments on 128 rats with brain ischemia/perfusion in conditions of modulation of the L-arginine-NO system were used to study changes in the concentrations of (a) lipid peroxidation products, i.e., diene conjugates, malonic dialdehyde, and Schiff bases, and (b) antioxidant protection factors, i.e., retinol, alpha-tocopherol, and SH-groups. Administration of L-arginine and NO synthase inhibitors, i.e., the non-selective inhibitor N(omega)-nitro-L-arginine methyl ester, the selective neuronal NO synthase inhibitor 7-nitroindasole, and the selective inhibitor of inducible NO synthase S-methylisothiourea, established that oxidative stress in rats with brain ischemia/perfusion is NO-dependent. NO formed by the various isoforms of NO synthase had different roles: hyperactivation of neuronal NO synthase was responsible for oxidative stress in both periods of brain ischemia/reperfusion, while increased inducible NO synthase activity was responsible in the late period.

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Background: Nitric oxide (NO) is one of the most important biologic messengers and takes part in the development of fever. It can influence on the body prooxidant-antioxidant balance by different ways including interaction with hemoglobin (Hb). Methods: The effects of nitric oxide synthesis inhibition on the febrile response, hemoglobin-oxygen affinity and parameters of lipid peroxidation were studied in rabbits with fever. The fever was induced by intravenous administration of lipopolysaccharide from Salmonella typhi (0.6 μg/kg). Mixed venous blood was taken before the administration and 60, 120 and 180 min after it. The following parameters were measured: half-saturation oxygen pressure (P₅₀), concentrations of conjugated dienes, Schiff bases and α-tocopherol in plasma and red blood cells, and activity of catalase in red blood cells. Results: The intravenous administration of the nitric oxide synthase inhibitor (N^ω-nitro-L-arginine; 5·10^–3 M) reduced the lipopolysaccharide-induced rise in body temperature. After 180 min the actual P₅₀ had decreased from 35.0 ± 1.7 to 29.4 ± 1.3 mm Hg. An increase in the lipid peroxidation parameters and a decrease of the antioxidant system indices were observed. The administration of L-arginine to prevent nitric oxide synthase inhibition was accompanied by a shift of the oxyhemoglobin dissociation curve rightwards, more marked activation of the free radical processes and a greater elevation of body temperature. The multiple regression analysis showed a close linear correlation between P₅₀ and conjugated dienes, Schiff bases, α-tocopherol and catalase. Conclusion: These results suggest that the increased hemoglobin-oxygen affinity found after the inhibition of nitric oxide synthesis lowers the oxygen flow to tissues and its fraction utilized in free radical oxidations, which finally causes a reduction of the fever response to the lipopolysaccharide.

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