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.
- CGRP (calcitonin gene-related peptide)
- Endothelium dependent
- Mesenteric resistance artery, (Rat)
- Thromboxane A
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