Cardiac allograft vasculopathy is the most aggressive form of atherosclerosis in humans and is the leading cause of death after the first year of heart transplantation. Endothelial dysfunction is a major contributing factor to the acceleration of coronary vascular disease in these individuals. A reflection of this endothelial dysfunction is the severe impairment in endothelium-dependent vasodil...

It has now become well accepted that nitric oxide (NO) has a key role to play in the signalling that takes place in plant cells. However, the sources of NO in plants has been hard to determine and there is considerable debate as to exactly how NO is made by plant cells. In animals nitric oxide synthase (NOS) enzymes have been characterised and such data has been used to inform the studies which...

Besides oxidizing L-arginine, neuronal NO synthase (NOS) NADPH-dependently reduces various electron acceptors, including cytochrome c and tetrazolium salts. The latter NADPH diaphorase reaction is used as a NOS-specific histochemical stain. Both reductase activities have been utilized to analyse electron transfer mechanisms within NOS. Basal L-arginine turnover by homodimeric NOS is enhanced by...

Inducible NO synthase (iNOS) is expressed by macrophages and smooth muscle cells in atherosclerotic lesions. Previously, we have established a mouse model for vein graft arteriosclerosis by grafting autologous jugular veins or vena cava to carotid arteries. Using this model, we studied the role of iNOS in the development of vein graft arteriosclerosis in iNOS / mice. Four weeks after grafting, ...

The nitric oxide synthases (NOSs) are dimeric flavocytochromes consisting of an oxygenase domain with cytochrome P450-like Cys-ligated haem, coupled to a diflavin reductase domain, which is related to cytochrome P450 reductase. The NOSs catalyse the sequential mono-oxygenation of arginine to N-hydroxyarginine and then to citrulline and NO. The constitutive NOS isoforms (cNOSs) are regulated by ...

Studies investigated the association between endothelial NO synthase gene polymorphisms and hypertension-reported contradicted or nonconclusive results. A meta-analysis of 35 genetic association studies that examined the relation between hypertension and the G894T, 4a/b, T786C, and G23T polymorphisms of the endothelial nitric oxide synthase gene was carried out. Subgroup analysis by ethnicity a...

Postural tachycardia syndrome (POTS) is a heterogeneous disorder characterized by an excessive rise in heart rate and symptoms consistent with cerebral hypoperfusion in the upright position. NO produced by endothelial NO synthase is a significant factor in the regulation of blood flow. Genetic polymorphisms in the promoter region (T-786C) and exon 7 (E298D) of the NO synthase isoform 3 gene aff...

For the specific analysis of endothelial NO synthase (eNOS) function in the coronary vasculature, we generated a mouse homozygous for a defective eNOS gene (eNOS-/-). Western blot as well as immunohistochemical staining revealed the absence of eNOS protein in eNOS-/- mice. Aortic endothelial cells derived from eNOS-/- mice displayed only background levels of NOx formation compared with wild-typ...

Evidence continues to accumulate on the importance of NO in angiogenesis.1–7 A number of angiogenic substances, including vascular endothelial growth factor (VEGF), stimulate production of NO in endothelial cells.8,9 In vivo biosynthesis of NO is essential for angiogenesis induced by tissue ischemia.3 Angiogenesis is severely impaired in ischemic hindlimb of endothelial NO synthase (eNOS)defici...

In a remarkable article published in this issue of Circulation Research, Ryoo et al1 propose endothelial arginase II as a novel target for the treatment of atherosclerosis. Actually, they already had done so 2 years ago, based on work mainly on cultured human aortic endothelial cells,2 which indeed appeared to provide an unexpected way to explain endothelial dysfunction in terms of NO productio...