Sian Claire Owen, Medical Journalist for Cardio Debate

The role nitric oxide (NO) plays in vasodilation is well established. However, much of the information to date has focused on the interaction of NO in the endothelial cells and vascular smooth muscle cells. A recent study – the first human study of its kind – published in the Hypertension journal looked at the potential role of NO produced in nerves, by neuronal NO synthase (NOS). Researchers from King’s College London were surprised to find that neuronal NO appears to play a larger role in blood pressure regulation than was previously recognised. [1]

This was small size investigation involving seventeen healthy normotensive men who were given intravenous infusions of S-methyl-L-thiocitrulline, an NOS-selective inhibitor that prevents the nerve endings from producing NO.

The highest dose (3.0µmol/kg over 10 minutes) of S-methyl-L-thiocitrulline produced a significant increase in systemic vascular resistance and diastolic blood pressure, compared with placebo. [1] Furthermore, S-methyl-L-thiocitrulline had no impact on radial artery flow-mediation, which is “an index of endothelial NOS activity”. [2]

The study was small, and conducted in healthy males aged 20 to 28 years. Therefore the next steps will be to replicate these results in different populations, including those with cardiovascular disease risk factors. [2]

Professor Ajay Shah, lead trial researcher from King’s College London and British Heart Foundation Chair of Cardiology at KCL stated in a press release that: “While we were surprised that stopping this enzyme would have some effect, we were surprised at how much influence it has on blood pressure”.

“Until now the majority of blood pressure drugs have focused on pathways other than NO. Establishing that nerves releasing NO influence blood pressure could eventually lead to the development of more effective treatment strategies  for patients.” [2]

Professor Phil Chowienczyk, Professor of Clinical Pharmacology at King’s College London and co-lead on the trial added that: “This link between release of nitric oxide from nerves and blood pressure is fascinating because it provides new insight into how blood pressure is controlled by the brain and into how mental health might affect blood pressure.’ [2]

This is an exciting discovery that will stimulate further research in an area of major importance in cardiovascular medicine.


  1. Blood pressure in healthy humans is regulated by neuronal NO synthase. Shabeeh H, Khan S, Jiang B, et al., Hypertension 2017; 69: 970-6.