Endothelium-derived C-type natriuretic peptide offsets the pathogenesis of pulmonary hypertension

mice exposed to SuHx, whereas global deletion of NPR-C specifically exacerbated the development of RVH and fibrosis without altering RVSP. In contrast, loss of cardiomyocyte-derived CNP did not result in a significant adverse phenotype. Pharmacological CNP administration significantly reduced RVSP and promoted anti-proliferative, anti-remodeling signaling in the cardiopulmonary circulation. These data elucidate the protective role of endogenous CNP signaling against the development of PH and provide preliminary evidence for the therapeutic potential of targeting CNP-dependent pathways, including both cognate NPR-B and NPR-C, in the context of pulmonary vascular disease and RV remodeling.