Abstract

DELMONTE¹, José A.. Nueva clase de fármacos para la hipertensión arterial pulmonar y la hipertensión pulmonar tromboembólica crónicaNew class of drugs for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Insuf. card. [online]. 2016, vol.11, n.3, pp.130-149. ISSN 1852-3862.

In the last fifteen years there were major discoveries in basic and clinical research in advancing the understanding of the pathophysiology, diagnosis and treatment of pulmonary arterial hypertension (PAH). Nitric oxide (NO) activates soluble guanylate cyclase (sGC), thereby catalyzing cyclic guanosine monophosphate (cGMP) synthesis. cGMP causes vasodilation and may inhibit vascular smooth muscle cell proliferation and platelet aggregation. The NO-sGC-cGMP pathway is disordered in PAH, a syndrome in which increased pulmonary vascular resistance, inflammation, and thrombosis lead to death from right heart failure. Expression of sGC is increased in PAH but its function is reduced by decreased NO bioavailability, sGC oxidation, and the related loss of sGC's heme group. The sGC modulators increase cGMP synthesis for the treatment of PAH. Riociguat is the first member of a new class of drugs sGC stimulators, causing vasodilation. Currently riociguat is approved for PAH and inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent / recurrent after surgery, with the aim of improving exercise capacity, functional class, and time delay in clinical deterioration. Riociguat is the first drug that has shown clinical benefits in CTEPH, an entity for which there was no specific drug treatment authorized. Its main serious adverse effect is dose-dependent hypotension. In this review, the pulmonary hypertension classification is update, particularly PAH, histology, pathophysiological mechanisms, especially the NO pathway, sGC and their modulators, cGMP and its role in PAH; and finally, clinical trials of sGC stimulators are summarized, with a focus on riociguat.

Keywords : Pulmonary arterial hypertension; Chronic thromboembolic pulmonary hypertension; Histology; Pathophysiological mechanisms; Nitric oxide; Soluble guanylate cyclase; cGMP; Modulators of sGC; Riociguat.

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