Tyrosine kinase inhibitors relax pulmonary arteries in human and murine precision-cut lung slices.

Annette Dorothea RiegNina A BüntingChristian CranenSaid SuleimanJan W SpillnerHeike SchnöringThomas SchröderSaskia von StillfriedTill BraunschweigPaul W ManleyGereon SchälteRolf RossaintStefan UhligChristian Martin

Published in: Respiratory research (2019)

TKIs relax pre-constricted PAs/PVs from both, mice and humans. In human PAs, the activation of K+-channels and the generation of cAMP are relevant for TKI-induced relaxation. Vice versa, PDGF-BB contracts PAs/PVs (human/mice) due to PDGFR. In murine PAs, PDGF-BB-induced contraction depends on intracellular calcium. So, PDGFR regulates the tone of PAs/PVs. Since TKIs combine relaxant and antiproliferative effects, they may be promising in therapy of PAH.

Keyphrases

endothelial cells
high glucose
induced pluripotent stem cells
diabetic rats
pulmonary hypertension
metabolic syndrome
oxidative stress
vascular smooth muscle cells
angiotensin ii
blood flow