![]() ![]() Prostacyclin or prostanoid is produced in the endothelium and it is a potent vasodilator in the pulmonary vasculature ( Gryglewski, 2008). Drugs acting on these pathways are summarized in Table 1. These are the prostacyclin, nitric oxide, and endothelin pathways. Current Clinical Therapy in Pulmonary Arterial HypertensionĬurrent PAH therapy focuses on three main pathways. This review seeks to summarize the research progress of PAH regarding to NO pathway, discuss the critical role of NO pathway in understanding the pathophysiology of PAH and new drug development. Meanwhile, novel compounds targeting on NO pathway exhibits great potential in development of next generation therapy medications. Phosphodiesterase-5 (PDE-5) inhibitors and soluble guanylate cyclase stimulators are the current drug classes acting on this pathway. Many molecular pathways have been linked to the development and treatment of PAH.It has been revealed that the nitric oxide (NO) pathway plays a very essential and central role in regulating vascular tone in the pulmonary circulatory system by interacting with other crucial signaling pathways. They reduce morbidity and only slightly improve survival with no effect on PAH mortality rate. ![]() Enormous progress has been made in the therapeutic practice of PAH in the past decades but there is still a long way to go because none of these present drugs are curative. Idiopathic PAH is the most common type of PAH in western countries with congenital heart disease-related PAH being the most prevalent in Asia ( Humbert et al., 2006 Lim et al., 2019).Ĭurrently approved PAH drugs such as prostacyclin analogues, endothelin receptor antagonists and phosphodiesterase-5 (PDE-5) inhibitors aim to control pulmonary vascular tone ( Olsson and Hoeper, 2009). There are different categories in PAH including idiopathic PAH, heritable PAH, drug or toxin-induced PAH and PAH associated with connective tissue disease, human immunodeficiency virus infection, portal hypertension, congenital heart disease and schistosomiasis ( Galiè et al., 2016). Generally, the major pathological changes of PAH are vasoconstriction and vascular remodelling of the small pulmonary arteries ( Tuder et al., 2009) involving the thickening of the intima-media, smooth muscle cell proliferation, endothelial cell proliferative lesions formation, vascular inflammation and immune dysregulation ( Tuder et al., 2007 Price et al., 2012 Humbert et al., 2019). Pulmonary arterial hypertension (PAH) is a fatal disease characterized by an increase in pulmonary arterial pressure with subsequent right ventricular failure and death ( Rosenkranz, 2015). Understanding such interactions could be helpful in the discovery of new drug that provide better clinical outcomes. Furthermore, the NO pathway is found to interact with other crucial pathways. Meanwhile, several novel compounds targeting on NO pathway exhibits great potential to become future therapy medications. Many of the essential drugs used in the management of PAH act on this pathway highlighting its significant role in PAH. Studies from clinical and non-clinical experiments have revealed that the nitric oxide (NO) pathway is one of the key pathways underlying the pathophysiology of PAH. Research in recent years has produced various therapeutic options for its clinical management but the high mortality even under treatment remains a big challenge attributed to the complex pathophysiology. Pulmonary arterial hypertension (PAH) is a severe disease with a resultant increase of the mean pulmonary arterial pressure, right ventricular hypertrophy and eventual death. 3Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, China.2Department of Health Management, The Third Xiangya Hospital, Central South University, Changsha, China.1Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha, China.Abraham Tettey 1, Yujie Jiang 1, Xiaohui Li 1,3 and Ying Li 2,3* ![]()
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