TY - JOUR
T1 - Triphasic vascular responses to bradykinin in the mesenteric resistance artery of the rat
AU - Nawa, Hideki
AU - Kawasaki, Hiromu
AU - Nakatsuma, Akira
AU - Isobe, Sachiko
AU - Kurosaki, Yuji
N1 - Funding Information:
This study is supported in part by a Grant-in-Aid for Scientific Research from Ministry of Education, Science, Culture and Sport of Japan. Seratrodast was generously donated by Takeda Pharmaceutical, Japan. FR 172357 was generously donated by Fujisawa Pharmaceutical, Japan.
PY - 2001/12/14
Y1 - 2001/12/14
N2 - The vascular effects of bradykinin were studied in rat perfused mesenteric vascular beds with active tone. Bolus injections of bradykinin (1-1000 pmol) but not des-Arg9-bradykinin (bradykinin B1 receptor agonist) induced triphasic vascular responses: the initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. The triphasic vascular responses to bradykinin were abolished by FR 172357 (3-bromo-8-[2,6-dichloro-3-[N-[(E)-4-(N,N-dimethylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2-metylimidazo[1,2-a]pyridine) (bradykinin B2 receptor antagonist, 0.1 μM). Endothelium removal with sodium deoxycholate and Nw-nitro-L-arginine (300 μM) abolished the bradykinin-induced initial sharp vasodilation. Indomethacin (0.5 μM) and seratrodast (thromboxane A2 receptor antagonist, 0.5 and 5 μM) abolished the bradykinin-induced second vasoconstriction. The bradykinin-induced third vasodilation was abolished by capsaicin (1 μM) and calcitonin gene-related peptide (CGRP)-(8-37) (CGRP receptor antagonist, 0.5 μM). These findings suggest that the bradykinin-induced initial sharp vasodilation is endothelium dependent, that endogenous thromboxane A2 is involved in the second vasoconstriction, and that the third slow vasodilation is produced by activation of capsaicin-sensitive CGRP-containing nerves.
AB - The vascular effects of bradykinin were studied in rat perfused mesenteric vascular beds with active tone. Bolus injections of bradykinin (1-1000 pmol) but not des-Arg9-bradykinin (bradykinin B1 receptor agonist) induced triphasic vascular responses: the initial sharp vasodilation followed by transient vasoconstriction and subsequent gradual vasodilation. The triphasic vascular responses to bradykinin were abolished by FR 172357 (3-bromo-8-[2,6-dichloro-3-[N-[(E)-4-(N,N-dimethylcarbamoyl) cinnamidoacetyl]-N-methylamino]benzyloxy]-2-metylimidazo[1,2-a]pyridine) (bradykinin B2 receptor antagonist, 0.1 μM). Endothelium removal with sodium deoxycholate and Nw-nitro-L-arginine (300 μM) abolished the bradykinin-induced initial sharp vasodilation. Indomethacin (0.5 μM) and seratrodast (thromboxane A2 receptor antagonist, 0.5 and 5 μM) abolished the bradykinin-induced second vasoconstriction. The bradykinin-induced third vasodilation was abolished by capsaicin (1 μM) and calcitonin gene-related peptide (CGRP)-(8-37) (CGRP receptor antagonist, 0.5 μM). These findings suggest that the bradykinin-induced initial sharp vasodilation is endothelium dependent, that endogenous thromboxane A2 is involved in the second vasoconstriction, and that the third slow vasodilation is produced by activation of capsaicin-sensitive CGRP-containing nerves.
KW - Bradykinin
KW - CGRP (calcitonin gene-related peptide)
KW - Endothelium dependent
KW - Mesenteric resistance artery, (Rat)
KW - Thromboxane A
KW - Vasodilation
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U2 - 10.1016/S0014-2999(01)01513-8
DO - 10.1016/S0014-2999(01)01513-8
M3 - Article
C2 - 11755140
AN - SCOPUS:0035861916
VL - 433
SP - 105
EP - 113
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -