Bradykinin induces NO and PGF production via B receptor activation from cultured porcine basilar arterial endothelial cells.

Our previous in vitro study demonstrated that bradykinin (BK) induced relaxation and contraction of porcine basilar artery (PBA) mediated via activation of endothelial B receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H, respectively, but not thromboxane A. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH has different functionally active isoforms, including PGD, PGE, and PGF, we have not yet clarified which of them is responsible for BK-induced contraction. Therefore, we attempted to quantify NO and PG production from cultured porcine basilar arterial endothelial cells (PBAECs) and to identify which of the PGs was involved in this contraction. The cultured PBAECs produced NO spontaneously, and BK enhanced this production in a concentration-dependent manner. The NO synthase inhibitor Nω-nitro- l-arginine (L-NNA) and the B receptor antagonist HOE-140, but not the B receptor antagonist des-Arg, [Leu]-BK, completely abolished it. In a functional study, PGD, PGE, and PGF induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF > PGE > PGD. The cultured PBAECs produced PGD, PGE, and PGF spontaneously, and BK significantly enhanced the production of PGF, but not that of PGD and PGE. The B, but not B, antagonist completely abolished the BK-enhanced production of PGF. These results suggest that BK induces production of NO and PGF simultaneously from PBAECs via B receptor activation. [ABSTRACT FROM AUTHOR]