Abstract
Nitric oxide (NO) signaling plays a key role in modulating vascular tone and remodeling in the pulmonary circulation. The guanylate cyclase/cyclic guanylate monophosphate-signaling pathway primarily mediates nitric oxide signaling. This pathway is critical in normal regulation of the pulmonary vasculature, and is an important target for therapy in patients with pulmonary hypertension. In the pulmonary vasculature, degradation of cGMP is primarily regulated by PDE-5, and inhibition of this enzyme has important effects on pulmonary vasculature smooth muscle tone. Large randomized placebo-controlled trials of PDE-5 inhibitors demonstrated improved exercise capacity, hemodynamics and quality of life in adult patients with PAH. This chapter will discuss the mechanisms of NO signaling in the vasculature, characteristics of the PDE5-inhibitors approved for treatment of PH, and review available data on the use of phosphodiesterase inhibitors in PH.
Abbreviations
- 6MWD:
-
6-min walk distance
- ANP:
-
Atrial natriuretic peptide
- BNP:
-
Brain-type natriuretic peptide
- cAMP:
-
Cyclic adenosine monophosphate
- cGK:
-
cGMP-dependent protein kinases
- cGMP:
-
Cyclic guanosine monophosphate
- CNP:
-
C-type natriuretic peptide
- CrCL:
-
Creatinine clearance
- EMA:
-
European Medicines Agency
- eNOS:
-
Endothelial nitric oxide synthase
- FDA:
-
United States Food and Drug Administration
- GTP:
-
Guanosine triphosphate
- HFpEF:
-
Heart failure preserved ejection fraction
- HFrEF:
-
Heart failure reduced ejection fraction
- NO:
-
Nitric oxide
- PAH:
-
Pulmonary arterial hypertension
- PAP:
-
Pulmonary artery pressure
- PDE:
-
Phosphodiesterase
- PH:
-
Pulmonary hypertension
- PKG:
-
Protein kinase-G
- QOL:
-
Quality of life
- RHC:
-
Right heart catheterization
- RV:
-
Right ventricle
- sGC:
-
Soluble guanylate cyclase
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Cockrill, B.A., Waxman, A.B. (2013). Phosphodiesterase-5 Inhibitors. In: Humbert, M., Evgenov, O., Stasch, JP. (eds) Pharmacotherapy of Pulmonary Hypertension. Handbook of Experimental Pharmacology, vol 218. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38664-0_10
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