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# Soluble guanylate cyclase (sGC) stimulators

Drugs that switch on the nitric oxide receptor in blood vessels, raising cGMP and relaxing them. Used in pulmonary hypertension and heart failure.

Updated Nov 1, 2026

## What they are

Riociguat (pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension) and vericiguat (heart failure with reduced ejection fraction).

## Mechanism of action

Soluble guanylate cyclase is the receptor for nitric oxide: it makes cGMP, which relaxes smooth muscle. sGC stimulators bind the enzyme at a site separate from NO, stimulate it directly and make it more sensitive to the little NO that is present, which matters when NO is lacking.

Target: Soluble guanylate cyclase (NO receptor)

## Key points

- Never combined with nitrates, NO donors or PDE-5 inhibitors: severe hypotension (contraindicated).
- Never two sGC stimulators together.
- Embryo-fetal toxicity: contraindicated in pregnancy, with pregnancy tests and contraception.
- Main adverse effects: hypotension, dizziness, headache, dyspepsia, anaemia.
- They need the haem iron in its reduced form; sGC activators (in research) act on the oxidized enzyme.

## Drugs in this class

- [**Riociguat** An oral sGC stimulator that relaxes lung arteries through cGMP. Used in pulmonary arterial hypertension and chronic… Soluble guanylate cyclase (α1β1), the nitric oxide receptor](https://durgical.com/en/pharmacology/riociguat/)
- [**Vericiguat** An oral sGC stimulator added to standard therapy in heart failure with reduced ejection fraction after a recent… Soluble guanylate cyclase (α1β1), the nitric oxide receptor](https://durgical.com/en/pharmacology/vericiguat/)

## Test yourself

Think of the answer, then tap the question to see it.

## Why are sGC stimulators contraindicated with sildenafil or nitrates?

All raise cGMP: nitrates via NO, PDE-5 inhibitors by slowing its breakdown, so the combination causes severe hypotension.

## How does an sGC stimulator differ from a nitrate?

A nitrate supplies NO; an sGC stimulator acts on the enzyme directly, at its own site, and sensitizes it to NO.

## Which two conditions does riociguat treat?

Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (CTEPH).

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Riociguat: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a615005.html) (MedlinePlus (U.S. National Library of Medicine), 2023); [DailyMed - RIOCIGUAT tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8092c64b-e240-43c3-9d2e-e0dd7708d96f) (DailyMed (U.S. National Library of Medicine), 2026).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/soluble-guanylate-cyclase-stimulators/