Pharmacological Gq inhibition induces strong pulmonary vasorelaxation and reverses pulmonary hypertension

ABSTRACT: Abstract: Pulmonary arterial hypertension (PAH) is a life-threatening disease with limited survival. Herein, we propose the pharmacological inhibition of Gq proteins as a novel concept to counteract pulmonary vasoconstriction and proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in PAH. We demonstrate that the specific pan-Gq inhibitor FR900359 (FR) induced a strong vasorelaxation in large and small pulmonary arteries in mouse, pig and human subjects ex vivo. Vasorelaxation by FR proved at least as potent as the currently used triple therapy. We also provide in vivo evidence that local pulmonary application of FR prevented right ventricular systolic pressure increase in healthy mice as well as in mice suffering from hypoxia (Hx)-induced pulmonary hypertension (PH). I

SUBMITTER: Dr. Alexander Seidinger 

PROVIDER: S-SCDT-10_1038-S44321-024-00096-0 | biostudies-other |

REPOSITORIES: biostudies-other