Table 2:  Drug inhibitors for the 5 different mechanisms of action.


Drug Name

Type of Drug

Working Mechanism



Guanylate cyclase activators

This peptide elicits potent hypertensive and vasorelaxant effects in vivo and in vitro through an autocrine and paracrine fashion. In the arteries, it works through protein kinase A phosphorylation and increased cAMP and NO production, promoting vasodilation.



TRPC6 Inhibitor

TRPC family members play a role in the pathogenesis of familial PAH and IPAH. TRPC6 upregulation plays a role in PASMC proliferation. They regulate cellular Ca2+ flux either by acting as Ca2+ entry channels or by changing membrane potentials. SAR7334 works by blocking the Ca2+ channel thereby reducing the hypoxia-induced increases in pulmonary arterial hypertension.



Serotonin Inhibitor

Plasma serotonin is increased in IPAH patients. Fluoxetine reduces hypoxic PH in rats, and targeted improvements in humans. The 5-hydroxytryptamine 2A (5-HT2A) receptor mediates serotonin-induced proliferation in rat pulmonary artery fibroblasts. Genetic deficiency of the 5-HT2B serotonin receptor reduces hypoxic PH in mice. SERT and the 5-HT receptors act coherently to mediate the proliferative effects of serotonin on PASMCs.



Transcription factor Inhibitor

Ca2+ regulated transcription factor nuclear factor of activated T cells isoform c3 (NFAT c3) is required for chronic hypoxia-induced PH in mice. NFAT c3 activation leads to proliferative response followed by recovery of contractile phenotype and hypertrophy of PASMC. It was recently demonstrated that RhoA/Rho kinase-dependent actin cytoskeleton remodeling is required for ET-1-mediated NFATc3 activation in PASMC from chronically hypoxic PH mice.



PDGF Inhibitor

Imatinib was found to block the PDGFR and improve experimental PH. Administration of imatinib and other PH drugs and suppression of GCC-proliferation by TS-1 resulted in normalization of hemodynamics, the lung perfusion scintigram, and arterial oxygen saturation.


Rho kinase inhibitors

Rho Kinase Inhibitors

In the vascular wall, ROCK mediates vascular smooth muscle contraction, actin cytoskeleton organization, cell adhesion, and motility. ROCK is also involved in vascular inflammation and remodeling, through Rock inhibitors have the ability produce endothelian-1, inhibition of downstream GPCR, and function in the cGMP pathway/NO pathway.