ICD-10 Specific code P29.3: Persistent fetal circulation

Nitric oxide is a compound produced by many cells of the body. It relaxes vascular smooth muscle by binding to the haeme moiety of cytosolic guanylate cyclase. When inhaled, nitric oxide produces selective pulmonary vasodilation.

Sildenafil is a potent and selective inhibitor of cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type 5 (PDE5), the enzyme that is responsible for degradation of cGMP. Apart from the presence of this enzyme in the corpus cavernosum of the penis, PDE5 is also present in the pulmonary vasculature. Sildenafil, therefore, increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation.

Sitaxentan is a potent (Ki 0.43 nM) and highly selective ETA antagonist (approximately 6,500-fold more selective for ETA as compared to ETB). Endothelin-1 (ET-1) is a potent vascular paracrine and autocrine peptide in the lung, and can also promote fibrosis, cell proliferation, cardiac hypertrophy, and remodelling and is pro-inflammatory. ET-1 actions are mediated through endothelin A (ETA) and endothelin B receptors (ETB). ET-1 concentrations are elevated in plasma and lung tissue of patients with pulmonary arterial hypertension (PAH), as well as other cardiovascular disorders and connective tissue diseases.