Functional characterization of the mechanisms underlying bradykinin-induced relaxation in the isolated rat carotid artery.
This work aimed to functionally characterize the mechanisms underlying the relaxation induced by bradykinin (BK) in the rat carotid artery. Vascular reactivity experiments, using standard muscle bath procedures, showed that BK (0.1 nmol/L-3 mumol/L) induced relaxation of phenylephrine-pre-contracted rings in a concentration-dependent manner. Endothelial removal strongly attenuated BK-induced relaxation. HOE-140, the selective antagonist of bradykinin B(2) receptors concentration-dependently reduced the relaxation induced by BK. Pre-incubation of endothelium-intact rings with L-NAME (100 micromol/L), a non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (100 micromol/L), a selective inhibitor of the eNOS or 7-nitroindazole (100 micromol/L), the selective inhibitor of nNOS, reduced BK-induced relaxation. Conversely, 1400 W (10 nmol/L), a selective inhibitor of iNOS, did not alter the relaxation induced by BK. Surprisingly, indomethacin (10 micromol/L) a non-selective inhibitor of cyclooxygenase (COX) increased BK-induced relaxation in endothelium-intact but not denuded rings. Neither SQ29548 (3 micromol/L), a competitive antagonist of PGH(2)/TXA(2) receptors nor AH6809 (10 micromol/L), an antagonist of PGF(2alpha) receptors significantly altered the relaxation induced by BK in endothelium-intact rings. The combination of SQ29548 and AH6809 increased BK-induced relaxation. The present study shows that the vasorelaxant action displayed by BK in the rat carotid is mediated by endothelial B(2) receptors and the activation of the NO pathway. The major finding of this work is that it demonstrated functionally that endothelial-derived vasoconstrictor prostanoids (probably PGH(2), TXA(2) and PGF(2alpha)) counteract the vasorelaxant action displayed by BK.
Tirapelli
Carlos R
CR
Department of Psychiatric Nursing and Human Sciences, College of Nursing of Ribeirão Preto, University of São Paulo (USP), SP, Brazil.
Bonaventura
Daniella
D
de Oliveira
Ana M
AM
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065094:Bradykinin B2 Receptor Antagonists; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007097:Imines / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000502:physiology; D014664:Vasodilation; D044004:Xanthones / Q000494:pharmacology
D065094:Bradykinin B2 Receptor Antagonists; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D007097:Imines; D007191:Indazoles; C496401:N-((3-(aminomethyl)phenyl)methyl)ethanimidamide; D043782:Receptor, Bradykinin B2; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; C065679:icatibant; C045749:SQ 29548; D019001:Nitric Oxide Synthase; D001920:Bradykinin; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin