Triphasic vascular responses to bradykinin in the mesenteric resistance artery of the rat

• Published in: European journal of pharmacology 2001-12, Vol.433 (1), p.105-113
• Main Authors: Nawa, Hideki, Kawasaki, Hiromu, Nakatsuma, Akira, Isobe, Sachiko, Kurosaki, Yuji
• Format: Article
• Language: English
• Subjects: Animals; Benzoquinones - pharmacology; Biological and medical sciences; Blood vessels and receptors; Bradykinin; Bradykinin - analogs & derivatives; Bradykinin - pharmacology; Calcitonin Gene-Related Peptide - pharmacology; Capsaicin - pharmacology; CGRP (calcitonin gene-related peptide); Endothelium dependent; Endothelium, Vascular - physiology; Fundamental and applied biological sciences. Psychology; Heptanoic Acids - pharmacology; Indomethacin - pharmacology; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; Mesenteric resistance artery; Nitroarginine - pharmacology; Peptide Fragments - pharmacology; Perfusion; Pyridines - pharmacology; Rat; Rats; Rats, Wistar; Thromboxane A 2; Vascular Resistance; Vasodilation; Vertebrates: cardiovascular system
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(01)01513-8

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-Arg 9-bradykinin (bradykinin B 1 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 B 2 receptor antagonist, 0.1 μM). Endothelium removal with sodium deoxycholate and N w-nitro- l-arginine (300 μM) abolished the bradykinin-induced initial sharp vasodilation. Indomethacin (0.5 μM) and seratrodast (thromboxane A 2 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 A 2 is involved in the second vasoconstriction, and that the third slow vasodilation is produced by activation of capsaicin-sensitive CGRP-containing nerves.