Plasma nitrite/nitrate levels: a new biomarker for pulmonary arterial hypertension?

The role of endothelial-derived nitric oxide (NO) and its downstream signalling pathways in modulating vascular tone and remodelling has been one of the most intriguing areas of vascular biology over the last quarter of a century. Its identification as the endothelial-derived relaxing factor responsible for relaxation of vascular smooth muscle led to the designation of NO as the “molecule of the year” by the journal Science in 1992 [1], and to a Nobel Prize in Physiology or Medicine for L.J. Ignarro, R.F. Furchgott and F. Murad in 1998. It is now well appreciated that the vascular endothelium, in response to a variety of stimuli, synthesises NO from l-arginine by activation of endothelial-derived NO synthase (eNOS), which then diffuses to adjacent vascular smooth muscle cells and activates soluble guanylate cyclase (sGC) leading to synthesis of cyclic guanosine monophosphate (cGMP). The increase in cytoplasmic levels of this secondary messenger activates a variety of mechanisms that decrease intercellular calcium and dephosphorylate the myosin light chain. The overall result is a potent mechanism by which the endothelium can induce vascular smooth muscle relaxation [2]. Plasma nitrate/nitrite levels are lower in patients with pulmonary hypertension and correlate with disease severity <http://ow.ly/JzYD304gWv4>