title: Triphasic vascular responses to bradykinin in the mesenteric resistance artery of the rat.
abstract: 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 microM). Endothelium removal with sodium deoxycholate and N(w)-nitro-L-arginine (300 microM) abolished the bradykinin-induced initial sharp vasodilation. Indomethacin (0.5 microM) and seratrodast (thromboxane A(2) receptor antagonist, 0.5 and 5 microM) abolished the bradykinin-induced second vasoconstriction. The bradykinin-induced third vasodilation was abolished by capsaicin (1 microM) and calcitonin gene-related peptide (CGRP)-(8-37) (CGRP receptor antagonist, 0.5 microM). 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.
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nawa
authors.forename: H
authors.initials: H
authors.lastname: Kawasaki
authors.forename: A
authors.initials: A
authors.lastname: Nakatsuma
authors.forename: S
authors.initials: S
authors.lastname: Isobe
authors.forename: Y
authors.initials: Y
authors.lastname: Kurosaki
mesh_terms: D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014655:Vascular Resistance
chemical_list: D016227:Benzoquinones; C106745:FR 167344; D006538:Heptanoic Acids; D010446:Peptide Fragments; D011725:Pyridines; C058636:calcitonin gene-related peptide (8-37); C024626:bradykinin, des-Arg(9)-; D019335:Nitroarginine; C060230:seratrodast; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin; D007213:Indomethacin