How does nitric oxide (NO) affect the body?

From the Guidelines

Nitric oxide (NO) is a crucial signaling molecule that affects multiple bodily systems, primarily functioning as a vasodilator to improve blood flow and lower blood pressure, with significant impacts on cardiovascular, immune, and respiratory systems, as well as neurotransmission and infection control. The effects of NO on the body are multifaceted, including the relaxation of blood vessels, prevention of blood clot formation, reduction of inflammation in blood vessels, and protection against atherosclerosis in the cardiovascular system 1. In the immune system, NO helps fight infections by killing bacteria and other pathogens, while in the respiratory system, it relaxes bronchial muscles and regulates airway tone 1. The body produces NO naturally through enzymes called nitric oxide synthases, using the amino acid L-arginine as a precursor, and some medications, such as nitroglycerin for angina and sildenafil for erectile dysfunction, leverage NO's effects 1. Key aspects of NO's role in the body include:

• Vasodilation and improved blood flow
• Anti-inflammatory effects
• Antimicrobial properties
• Neurotransmission and neural development
• Regulation of airway tone and bronchial muscles Some of the key evidence supporting the role of NO in the body comes from studies on its use in pulmonary hypertension, where it has been shown to have selective and potent pulmonary vasodilator effects 1, and in asthma, where high levels of NO in exhaled breath have been linked to airway inflammation 1. Overall, the current understanding of NO's effects on the body prioritizes its role as a vasodilator and its potential benefits in improving cardiovascular health and reducing inflammation, while also acknowledging its complex interactions with various bodily systems. Given the most recent and highest quality evidence, the use of inhaled nitric oxide (iNO) for certain respiratory conditions, such as pulmonary hypertension, is supported, with typical dosages ranging from 5-20 ppm 1.

From the FDA Drug Label

Nitric oxide relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine 3',5'-monophosphate, which then leads to vasodilation When inhaled, nitric oxide selectively dilates the pulmonary vasculature, and because of efficient scavenging by hemoglobin, has minimal effect on the systemic vasculature INOmax appears to increase the partial pressure of arterial oxygen (PaO2) by dilating pulmonary vessels in better ventilated areas of the lung, redistributing pulmonary blood flow away from lung regions with low ventilation/perfusion (V/Q) ratios toward regions with normal ratios.

Effects of Nitric Oxide on the Body:

• Vasodilation: Nitric oxide causes relaxation of vascular smooth muscle, leading to vasodilation.
• Increased Oxygenation: Nitric oxide increases the partial pressure of arterial oxygen (PaO2) by dilating pulmonary vessels in better ventilated areas of the lung.
• Minimal Systemic Effect: Due to efficient scavenging by hemoglobin, nitric oxide has minimal effect on the systemic vasculature.
• Pulmonary Vasodilation: Nitric oxide selectively dilates the pulmonary vasculature, improving oxygenation in conditions such as persistent pulmonary hypertension of the newborn (PPHN) 2.

From the Research

Physiological Effects of Nitric Oxide

• Nitric oxide (NO) is a key player in the regulation of blood flow and pressure, maintaining a vasodilator tone that is essential for the regulation of blood flow and pressure 3.
• In the brain, nitric oxide acts as a mediator of cell-cell signalling, and in the peripheral nervous system, it is released from many nerves previously classified as non-adrenergic and non-cholinergic 3.
• Nitric oxide is also important in the pulmonary circulation, where it helps to maintain normal vascular tone and prevent pulmonary hypertension 4.

Therapeutic Effects of Nitric Oxide

• Nitric oxide has been shown to be effective in the treatment of pulmonary hypertension, and it remains an effective option in the management of this condition 5.
• Inhaled nitric oxide has been used to treat chronic pulmonary hypertension and adult respiratory distress syndrome, and it has been shown to improve cardiopulmonary hemodynamics 3.
• Nitric oxide donors have also been used to treat hypertension, atherosclerosis, gastrointestinal and genitourinary disorders, and they have been shown to be effective in improving symptoms and outcomes in these conditions 3.

Nitric Oxide Pathway and Pulmonary Arterial Hypertension

• The nitric oxide pathway is mediated by the guanylate cyclase/cyclic guanylate monophosphate pathway, and it plays a key role in the regulation of pulmonary vasoregulation 6.
• Phosphodiesterase inhibitors, such as sildenafil, have been shown to be effective in the treatment of pulmonary arterial hypertension, and they work by increasing the levels of cyclic guanylate monophosphate and promoting vasodilation 6.
• Nitric oxide, oxidative stress, and inflammation all contribute to the development and progression of pulmonary arterial hypertension, and targeting these factors may provide new therapeutic opportunities for the treatment of this condition 7.