Constitutive and inducible nitric oxide synthases incorporate molecular oxygen into both nitric oxide and citrulline.

Leone, Anna; Palmer, Richard; Knowles, Richard G.; Francis, Peter; Ashton, David; Moncada, Salvador

doi:10.1016/s0021-9258(18)54352-0

Cited by 261 publications

(31 citation statements)

References 32 publications

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“…5 Under normal conditions, cNOS produces NO and L-citrulline from L-arginine and O 2 . 6 Isolated cNOS, when activated in L-arginine-starved environments, can still receive electrons from NADPH and donate them to its substrate O 2 , resulting in its one electron reduction to superoxide (O 2 which produces superoxide instead of NO. O 2 Ϫ generation by cNOS appears to account for about 70% of the O 2 Ϫ produced after reperfusion.…”

mentioning

confidence: 99%

Combined l-arginine and antioxidative vitamin treatment mollifies ischemia-reperfusion injury of skeletal muscle

Nanobashvili

Neumayer

Fuegl

et al. 2004

Journal of Vascular Surgery

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Enhanced production of superoxide in L-arginine-depleted environments and concomitant reduction of nitric oxide (NO) concentration are involved in ischemia-reperfusion (I/R) injury. Treatment with L-arginine or antioxidative vitamins alone and in combination was used to mollify I/R injury in skeletal muscle. Untreated rabbits were compared with those treated with L-arginine/antioxidative vitamin cocktail Omnibionta only, or a combination of L-arginine/ antioxidative vitamins during hind limb I/R (2.5 hours/2 hours). NO was continuously measured in vivo. Plasma malondialdehyde (MDA) served as the measure of oxygen free radical formation. Interstitial edema formation, microvessel diameter alterations, microvessel plugging, and blood flow changes were used as indicators of I/R injury. The MDA level in untreated animals 2 hours after reperfusion was significantly higher than in control animals (0.81 micromol/L +/- 0.14 micromol/L vs 0.57 micromol/L +/- 0.11 micromol/L; P<.05), indicating enhanced production of oxygen free radicals. This sequela paralleled the decreasing concentration of NO, which dropped below the detection limit (1 nmol/L) after reperfusion. Microvascular changes during I/R injury were expressed as a 40% decrease in microvessel diameter and adhesion of neutrophils in 20% of microvessels, which led to a consequent 60% reduction in blood flow, demonstrating "no reflow" (reperfusion failure after restoration of blood flow). The increase in the fraction of muscle interfiber area by 85% indicated prominent edema formation. Treatment with antioxidative vitamins alone had a minimally positive effect on edema formation and microvascular plugging, possibly by suppression of oxygen free radical production, as expressed by the reduction in plasma MDA levels. However, this therapy failed to preserve basal NO production and to protect from microvascular constriction and no reflow. Treatment with L-arginine alone had a stronger protective effect, maintaining basal NO production, further reduction of neutrophil plugging, abolition of microvascular constriction, and no reflow. The combination of antioxidative vitamins and L-arginine was the best treatment against I/R injury, expressed not only by the protection of microvessel constriction, but also by abolition of microvascular plugging, increase in NO production (68 nmol/L +/- 5 nmol/L) over the basal level (52 nmol/L +/- 7 nmol/L), and higher blood flow, as compared with treatment with L-arginine or antioxidative vitamins alone.

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mentioning

confidence: 99%

Combined l-arginine and antioxidative vitamin treatment mollifies ischemia-reperfusion injury of skeletal muscle

Nanobashvili

Neumayer

Fuegl

et al. 2004

Journal of Vascular Surgery

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“…We also attempted to identify the enzyme responsible for the generation of NO and in 1989 identified NO synthase, able to generate NO and L-citrulline from L-arginine . Soon afterwards we showed that the enzyme incorporated molecular oxygen into two steps of the process including the formation of L-citrulline (Leone et al 1991). Those experiments were published after similar results by Kwon et al (1990).…”

Section: Therapeutic Implications Of the Prostacyclin/txa 2 Balancementioning

confidence: 68%

Adventures in vascular biology: a tale of two mediators

Moncada

2006

Phil. Trans. R. Soc. B

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I would like to thank the Royal Society for inviting me to deliver the Croonian Lecture. In so doing, the Society is adding my name to a list of very distinguished scientists who, since 1738, have preceded me in this task. This is, indeed, a great honour. For most of my research career my main interest has been the understanding of the normal functioning of the blood vessel wall and the way this is affected in pathology. During this time, our knowledge of these subjects has grown to such an extent that many people now believe that the conquering of vascular disease is a real possibility in the foreseeable future. My lecture concerns the discovery of two substances, prostacyclin and nitric oxide. I would like to describe the moments of insight and some of the critical experiments that contributed significantly to the uncovering of their roles in vascular biology. The process was often adventurous, hence the title of this lecture. It is the excitement of the adventure that I would like to convey in the text that follows.

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“…At the same time, it was reported that high symmetric dimethylarginine levels were associated with significantly obstructive coronary artery disease (42). Arg can convert to Cit and NO by NO synthase in endothelial cells (43,44). To this end, ample evidence indicates that atherogenic oxidized low-density lipoprotein (ox-LDL) can inhibit endothelialderived NO, thus leading to leukocyte deposition, platelet adhesion, platelet aggregation, and subsequent release of vasoconstrictor species such as serotonin and TXA2 (45)(46)(47)(48), which lead to endothelial-dependent vasomotor abnormalities (49).…”

Section: Discussionmentioning

confidence: 96%

Characteristics of Blood Metabolic Profile in Coronary Heart Disease, Dilated Cardiomyopathy and Valvular Heart Disease Induced Heart Failure

Liu

et al. 2021

Front. Cardiovasc. Med.

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Purpose: Metabolic impairment is one key contributor to heart failure (HF) pathogenesis and progression. The major causes of HF, coronary heart disease (CHD), dilated cardiomyopathy (DCM), and valvular heart disease (VHD) remains poorly characterized in patients with HF from the view of metabolic profile. We sought to determine metabolic differences in CHD-, VHD-, and DCM-induced HF patients and identify significantly altered metabolites and their correlations.Procedure: In this study, a total of 96 HF cases and 97 controls were enrolled. The contents of 23 amino acids and 26 carnitines in fasting plasma were measured by a targeted liquid chromatography and mass spectrometry (LC-MS) approach.Results: Nine metabolites (Histidine, Arginine, Citrulline, Glutamine, Valine, hydroxyhexadecenyl-carnitine, acylcarnitine C22, hydroxytetradecanoyl-carnitine, and carnitine) were found to be related with the occurrence of HF. Arginine, Glutamine and hydroxytetradecanoyl-carnitine could effectively distinguish CHD and DCM patients, and hydroxytetradecanoyl-carnitine and aspartic acid were able to classify CHD and VHD cohorts.Conclusion: This study indicated that circulating amino acids and long-chain acylcarnitine levels were closely associated with progression of heart failure. Monitoring these metabolic alterations by LC-MS may help the differentiation of CHD, VHD, and DCM in the early stage, and provide new diagnostics targets or therapeutic interventions.

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Constitutive and inducible nitric oxide synthases incorporate molecular oxygen into both nitric oxide and citrulline.

Cited by 261 publications

References 32 publications

Combined l-arginine and antioxidative vitamin treatment mollifies ischemia-reperfusion injury of skeletal muscle

Combined l-arginine and antioxidative vitamin treatment mollifies ischemia-reperfusion injury of skeletal muscle

Adventures in vascular biology: a tale of two mediators

Characteristics of Blood Metabolic Profile in Coronary Heart Disease, Dilated Cardiomyopathy and Valvular Heart Disease Induced Heart Failure

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