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Nitric Oxide for Pulmonary Hypertension

Medically reviewed by Steven C. Pugliese, M.D.
Written by Emily Wagner, M.S.
Posted on November 22, 2021

Several classes of drugs are used in the treatment of pulmonary hypertension (PH), including vasodilators. Vasodilators work by opening the blood vessels to help blood flow. One specific type of vasodilator is inhaled nitric oxide (NO), which is used to help relieve high blood pressure in newborns, children, and adults with different types of PH.

What Is Nitric Oxide?

NO is a naturally occurring compound that relaxes and opens up blood vessels, which is important for controlling normal blood pressure levels in the body. Inhaled NO can serve as a selective pulmonary vasodilator: It can open up blood vessels only in the lungs while leaving the rest of the body unaffected. This is different from most PH treatments, which are systemic and affect the whole body.

NO moves into the bloodstream and travels to the muscles found in blood vessels (known as vascular smooth muscle), opening them up to allow more blood to flow through. As a result, your heart does not have to work as hard to pump blood, and your blood pressure will decrease.

How Is Nitric Oxide Used for Pulmonary Hypertension?

NO therapy was approved for use by the U.S. Food and Drug Administration (FDA) in 1999 for both treatments and research purposes. These treatments are well-established and have been used in surgeries and as emergency treatments.

NO is given as an inhaled gas that is breathed in through the nose and/or mouth, usually at a starting concentration of 5 to 20 parts per million (ppm). However, it can be increased to up to 80 ppm if needed. While you are undergoing NO therapy, your doctor will monitor how much oxygen is in your blood, the blood pressure within your lungs (pulmonary arterial pressure), and your whole-body blood pressure.

Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn

Persistent pulmonary hypertension of the newborn (PPHN) is a breathing condition that develops in newborn babies who have respiratory failure caused by PH. PPHN develops when the blood vessels in a newborn’s lungs do not open enough to let blood and oxygen flow through them. This can lead to low oxygen levels and can affect the brain and other organs. It is important to open the blood vessels as quickly as possible for this condition to ensure the baby is getting enough oxygen.

NO is one treatment used in PPHN that helps open the blood vessels in the lungs to improve blood flow. The baby inhales NO through their mouth and/or nose to reach the lungs. This may be used alongside a ventilator, which moves air in and out of the lungs to help them rest.

Nitric Oxide for Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a type of PH that occurs in children and adults. It is caused by several factors, including genetics, certain medications, and other underlying health conditions such as sleep apnea or autoimmune diseases.

Inhaled NO gas is used to treat PAH in both children and adults. However, some people respond to the treatment better than others. They are classified as either responders or nonresponders based on how well NO reduces the resistance of blood flow (pulmonary vascular resistance) and the blood pressure within the lungs’ arteries (mean pulmonary artery pressure).

NO can also be combined with other PH treatments to enhance its effects. For example, phosphodiesterase (PDE) inhibitors are used to stop enzymes from breaking down an important molecule, known as cyclic guanosine monophosphate (cGMP), that helps NO treatment work. The PDE inhibitor sildenafil helps NO work for longer to improve lung function in adults with PAH.

Nitric Oxide for Postoperative Pulmonary Hypertension

PH can develop after surgeries used to treat several conditions, such as:

  • Heart transplants
  • Congenital heart disease surgery
  • Placement of a left ventricular assist device (or LVAD), a medical device for people with heart failure

Inhaled NO gas has been found to treat PH that develops after surgery. It can also help prevent the need for other, more intense treatments. In addition, NO gas can be given before surgery to help prevent PH from developing.

Advantages and Disadvantages of Nitric Oxide Therapy

Inhaled medication can have special benefits that other systemic medications do not. For example, it is a selective therapy that only affects the lungs when breathed in. This means that NO can be given at high concentrations with fewer side effects than other treatments. Systemic vasodilators will open up blood vessels throughout the entire body, which can lead to low blood pressure and affect other organs.

Inhaled NO gas will open up only blood vessels in the lungs to help improve blood flow and oxygenation. Protein hemoglobin in the blood takes up NO gas quickly, so it becomes inactive before it can have any further effects.

However, inhaled therapies like NO gas have disadvantages. If a person has sensitive airways that are easily irritated, inhaling a gas may cause coughing or other breathing issues. Controlling exactly how much NO gas a person is receiving can be difficult, because everyone breathes at a different rate.

Talk With Others Who Understand

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Posted on November 22, 2021
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Steven C. Pugliese, M.D. is affiliated with the Hospital of the University of Pennsylvania in Philadelphia, serving as the director of the pulmonary embolism response team, co-director of the comprehensive pulmonary embolism program, and an assistant professor of clinical medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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