Simply say yes to NO? Nitric oxide (NO) sensor-based assessment of coronary endothelial function

Abstract

This editorial refers to ‘First evaluation of real-time nitric oxide changes in the coronary circulation in patients with non-ischaemic dilated cardiomyopathy using a catheter-type sensor’, by S. Takarada et al. doi:10.1093/eurheartj/ehq156 In 1980 Furchgott and Zawadzki published their observation on how removal of the endothelium abolishes acetylcholine-induced relaxation of vascular smooth muscle cells, which ignited a passionate search for an endothelium-derived vasorelaxing factor.1 Yet who would have thought in the beginning that the search was for a gas! Seven years later, Ignarro and co-workers identified nitric oxide (NO) as the endothelium-derived vasorelaxing factor.2 In the same decade, Murad's laboratory pointed out that NO activates the cytosolic (soluble) isoenzyme form of guanylate cyclase which increases cGMP synthesis and leads to the activation of cGMP-dependent protein kinase and ultimately reduces intracellular calcium concentration and elicits vascular smooth muscle relaxation.3 Closing the loop on endothelium-dependent vasorelaxation with these findings and discovering ‘nitric oxide as a signaling molecule in the cardiovascular system’, Robert Furchgott, Louis Ignarro, and Ferid Murad were awarded the Nobel Prize in Physiology/Medicine in 1998. NO's role in the physiology and pathology of the cardiovascular system is quite manifold and extends beyond its anatomical boundaries (Figure 1). In synoptic terms, NO is a multifunctional molecule that exerts anti-atherosclerotic properties in the vasculature and contributes to primarily the diastolic function of the myocardium.4,5 Abnormalities in the endogenous NO system have been found in various pathological conditions of the cardiovascular system including hypertension, atherosclerosis, and cardiomyopathies. … *Corresponding author. Tel: +1 507 255 4152, Fax: +1 507 255 2550, Email: lerman.amir{at}mayo.edu