Effect of Nitric Oxide Synthase Inhibition on Hemoglobin-Oxygen Affinity and Lipid Peroxidation in Rabbits during Fever

Abstract

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.

Blood oxygen transport and endothelial dysfunction in patients with arterial hypertension

“…The p50 value for SNO-Hb outside an erythrocyte is equal to 10 mmHg (Bonaventura et al, 1999), whereas that for a SNO-Hb solution -(with 30% nitrosylation of 93 cysteine) -to 4AE3 ± 0AE27 mmHg (Patel et al, 1999) and that for HbFe 2+ NOto 39AE6 ± 1AE5 mmHg (Kosaka & Seiyama, 1996). Their effect on the modulation of the blood oxygen-binding properties is manifested at high concentrations (5 and above%), and this may be important for gas exchange properties in capillaries (Zinchuk, 1999;Zinchuk & Dorokhina, 2002). Their effect on the modulation of the blood oxygen-binding properties is manifested at high concentrations (5 and above%), and this may be important for gas exchange properties in capillaries (Zinchuk, 1999;Zinchuk & Dorokhina, 2002).…”

“…The blood SNO-Hb and HbFe 2+ NO concentrations are such that either of these derivatives has on the average 1000 tetramers of haemoglobin, and this makes their effects on blood oxygen-binding properties relatively negligible under general conditions (Jia et al, 1996;Yonetani et al, 1998), but at NO concentrations above physiological conditions (at low pH, on addition of inosytolhexaphosphate, at low temperature) this is quite possible. Their effect on the modulation of the blood oxygen-binding properties is manifested at high concentrations (5 and above%), and this may be important for gas exchange properties in capillaries (Zinchuk, 1999;Zinchuk & Dorokhina, 2002).…”

Molecular mechanisms of nitric oxide deposition in erythrocytes

“…Вивчення взаємодії гемоглобіну з NO є надзвичайно актуальною проблемою, оскільки оксид азоту вищу високу спорідненість до гемової групи дезоксигемоглобіну, ніж О 2 та СО. Це дає змогу припускати його конкурування з киснем за відповідні ділянки на молекулах частково оксигенованого гемоглобіну [63]. Взаємодія NO з гемоглобіном в еритроцитах важлива для регуляції цих обох молекул in vivo.…”

“…NO проникає крізь клітинну мембрану за допомогою спеціального переносника білка АЕ1 або аніон-обмінника. Проникність еритроцитарної мембрани для NO порівняно невисока, що впливає на його біодоступність і взаємодію оксиду азоту з гемоглобіном [63]. Припускають існування цитоскелетного бар'єру для дифузії NO, який реалізується через спеціальні міжбілкові пори в еритроцитарній мембрані, стан деяких регулюється і, відповідно, змінює вхід NO [47].…”

Stress‐ and lipopolysaccharide‐induced c‐fos expression and nNOS in hypothalamic neurons projecting to medullary raphe in rats: a triple immunofluorescent labeling study

“…Thus, exteroceptive stress but not inflammatory stress appears to engage nNOS-containing neurons in the DMH that project to the rRP, suggesting that different populations of neurons contributing to this pathway are activated in these settings. Although nitric oxide has been implicated in the modulation of fever induced by lipopolysaccharide or cytokines Roth et al, 1998b;Krukoff, 1999;Perotti et al, 1999;Zinchuk, 1999;De Paula et al, 2000;Soszynski, 2001;Kamerman et al, 2002;Steiner et al, 2002Steiner et al, , 2004Kozak & Kozak, 2003;Sanches et al, 2003;Gray et al, 2005), no study to date has examined the potential role of nitric oxide specifically in the DMH in any experimental model for stress or fever. However, microinjection of the nitric oxide donor molsidomine into either the posterior hypothalamus, a region posteriorly adjacent to the DMH, or the paraventricular hypothalamic nucleus, less than 1 mm anterior to the DA ⁄ DMH, reduced the tachycardia evoked by shaker stress in rats by nearly half (Hashiguchi et al, 1997).…”