How Do Soluble Guanylate Cyclase Stimulators Work?

Soluble guanylate cyclase (sGC) stimulators are medications used to treat heart failure and pulmonary arterial hypertension (PAH), a condition of high blood pressure in the arteries that carry deoxygenated blood from the heart to the lungs.

Soluble guanylate cyclase stimulators enhance the activity of sGC, an enzyme in the cardiopulmonary system that relaxes vascular smooth muscles, resulting in pulmonary vasodilation, reduced PAH, and improved cardiac output. Soluble guanylate cyclase is activated by nitric oxide released by the vascular inner wall (endothelium).

Nitric oxide (NO) binds to sGC and activates the synthesis of a signaling molecule known as cyclic guanosine monophosphate (cGMP), which in turn activates a cascade of downstream actions. The functions of cGMP include regulation of vascular tone, cardiac contraction, and remodeling.

Impairment in the functioning of the NO-sGC-cGMP pathway can lead to pulmonary arterial hypertension and heart failure. Soluble guanylate cyclase stimulators work in dual ways by directly stimulating sGC and also enhancing sGC’s sensitivity to nitric oxide.

Soluble guanylate cyclase stimulators are oral tablets prescribed in the treatment of the following conditions:

FDA-approved:

• To improve exercise capacity and delay disease progression in:
  • Pulmonary arterial hypertension
  • Chronic thromboembolic pulmonary hypertension (CTEPH)
• To reduce the risk of cardiovascular death and heart failure in patients hospitalized for a heart failure

Orphan designation:

• Systemic sclerosis (autoimmune connective tissue disease)
• Fontan-palliated patients (Fontan palliation is a type of surgical procedure performed for a congenital heart condition)

Side effects of soluble guanylate cyclase stimulators may include the following:

• Headache
• Dyspepsia (indigestion)
• Gastritis
• Dizziness
• Nausea
• Diarrhea
• Vomiting
• Hypotension (low blood pressure)
• Anemia
• Gastroesophageal reflux disease (GERD)
• Constipation
• Serious bleeding
• Hemoptysis (coughing up blood)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of soluble guanylate cyclase stimulator drugs include:

• Adempas
• riociguat
• vericiguat
• Verquvo