Mechanism of contractile responses to bradykinin in canine basilar arteries.
This study was undertaken to investigate the role of endothelium in the modulation of vascular responses to bradykinin and to elucidate the receptor types and mechanism of action of bradykinin in isolated basilar artery. The results showed a contractile response to bradykinin in basilar artery. This contractile response to bradykinin was partially modulated by endothelium in a dose-dependent manner. In addition, both des-Arg9-[Leu8]bradykinin and [d-Arg0,Hyp3,Thi5,8,D-Phe7]bradykinin significantly antagonized the responses to bradykinin. However, the blocking effect and the apparent affinity of [d-Arg0,Hyp3,Thi5,8,D-Phe7]bradykinin (pA2 = 9.6 +/- 0.4) were greater than those with des-Arg9-[Leu8]bradykinin (pA.2 = 7.8 +/- 0.3). These results suggest that two apparently distinct types of BK receptors may exist in basilar arteries. Furthermore, the contractile response to bradykinin in basilar artery was significantly inhibited by 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (10(-5) M), H-7 (10(-5) M) and TMB-8 (10(-5) M), but not by indomethacin (10(-5) M) or nordihydroquariaretic acid (10(-5) M). On the other hand, nifedipine, Ca(2+)-free medium, EGTA and Ca(2+)-free medium/EGTA significantly reduced the bradykinin-induced contraction, indicating that part of the contractile response of basilar artery to bradykinin is dependent on extracellular Ca2+. In conclusion, the mechanism of the contractile responses to bradykinin in basilar artery may involve increased intracellular Ca2+ levels acting on the BK1 and BK2 receptor, followed by activation of the phosphoinositide pathway and receptor-mediated Ca2+ channel.
Yen
M H
MH
Department of Pharmacology, National Defense Medical Center, Tapei, Taiwan.
Lai
C S
CS
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D009637:Masoprocol; D011493:Protein Kinase C; D001920:Bradykinin; D002118:Calcium; D007213:Indomethacin