Journal
HYPERTENSION
Volume 76, Issue 4, Pages 1055-1068Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.120.15856
Keywords
hypertension; mitochondria; nitric oxide; oxidoreductase; soluble guanylyl cyclase
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Funding
- Stichting Lijf en Leven (Rotterdam, the Netherlands) [60]
- Intracellular Therapies Inc. (New York)
- Sulfateq B.V. (Groningen, the Netherlands)
- Topconsortia voor Kennis en Innovatie Life Science and Health (TKI-LSH) [EMCLSH19013]
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For the treatment of systemic hypertension, pharmacological intervention in nitric oxide-cyclic guanosine monophosphate signaling is a well-explored but unexploited option. In this review, we present the identified drug targets, including oxidases, mitochondria, soluble guanylyl cyclase, phosphodiesterase 1 and 5, and protein kinase G, important compounds that modulate them, and the current status of (pre)clinical development. The mode of action of these compounds is discussed, and based upon this, the clinical opportunities. We conclude that drugs that directly target the enzymes of the nitric oxide-cyclic guanosine monophosphate cascade are currently the most promising compounds, but that none of these compounds is under investigation as a treatment option for systemic hypertension.
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