The Effects of Stable Bradykinin Receptor 2 Agonist B9972 on Pulmonary Vasculature in vitro and vivo

摘要

The nine-amino-acid vasoactive peptide bradykinin (BK) has a twofold action profile by exerting pathophysiological as well as pronounced beneficial physiological effects. Bradykinin plays a powerful role in angiogenesis and cardioprotection. Since bradykinin itself has a very short lifetime, we synthesized a novel stable B2-receptor agonist B9972 to study the effects of this compound on human pulmonary microvascular endothelial (HPMVEC) cells in vitro and in our animal model of severe pulmonary hypertension in vivo. Since bradykinin is known to stimulate angiogenesis, we used two inhibitors of angiogenesis: SU5416 that inhibits VEGFR1-3 and a broad spectrum tyrosine kinase inhibitor SU6668 that inhibits PDGFR, and to a lesser extent VEGFR-2.