Bradykinin induces NO and PGF2α production via B2 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 B2 receptors. The main relaxing and contracting factors appeared to be nitric oxide (NO) and prostaglandin (PG) H2, respectively, but not thromboxane A2. After obtaining these findings, we succeeded in cultivating endothelial cells isolated from the PBA. Although PGH2 has different functionally active isoforms, including PGD2, PGE2, and PGF2α, 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 B2 receptor antagonist HOE-140, but not the B1 receptor antagonist des-Arg(9), [Leu(8)]-BK, completely abolished it. In a functional study, PGD2, PGE2, and PGF2α induced concentration-dependent contractions in isolated porcine basilar arterial rings, the order of maximum contraction being PGF2α > PGE2 > PGD2. The cultured PBAECs produced PGD2, PGE2, and PGF2α spontaneously, and BK significantly enhanced the production of PGF2α, but not that of PGD2 and PGE2. The B2, but not B1, antagonist completely abolished the BK-enhanced production of PGF2α. These results suggest that BK induces production of NO and PGF2α simultaneously from PBAECs via B2 receptor activation.
Department of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima, 890-0065, Japan.
Md Zahorul
MZ
Islam
Kaori
K
Miyagi
Tsukasa
T
Matsumoto
Ha Thi Thanh
HT
Nguyen
Emi
E
Yamazaki-Himeno
Mitsuya
M
Shiraishi
Atsushi
A
Miyamoto
D000818:Animals; D001488:Basilar Artery / Q000166:cytology; D001920:Bradykinin / Q000378:metabolism*; D002478:Cells, Cultured; D015237:Dinoprost / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D013552:Swine
D043782:Receptor, Bradykinin B2; D009569:Nitric Oxide; D015237:Dinoprost; D001920:Bradykinin