Nitric oxide deficiency is a primary driver of hypertension

[Display omitted] Hypertension remains a global health crisis. High blood pressure is the number one modifiable risk factor in the onset and progression of cardiovascular disease. Despite many different classes of drug therapies approved for hypertension, the use of polypharmacy and recommendations on lifestyle modification, many patients still suffer from uncontrolled or unmanaged hypertension. Nitric oxide is a naturally produced vasodilator that controls and regulates vascular tone and therefore controls and regulates blood pressure. Research over the past 40 years reveals that loss of nitric oxide production, termed endothelial dysfunction, is the earliest event in the development of hypertension. Strategies aimed at preventing the loss of nitric oxide production and/or therapeutic strategies designed to restore nitric oxide production will likely have a positive effect on patients’ health and lead to better management of blood pressure. This review article will focus on the loss of nitric oxide production as the primary contributor to hypertension and also discuss safe and clinically proven strategies to restore nitric oxide production and recapitulate nitric oxide based signaling in humans.