Triphasic vascular responses to bradykinin in the mesenteric resistance artery of the rat.
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.
Nawa
H
H
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan.
Kawasaki
H
H
Nakatsuma
A
A
Isobe
S
S
Kurosaki
Y
Y
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
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