Endothelial kinin B(1)-receptors are induced by myocardial ischaemia-reperfusion in the rabbit.
Kinin B1-receptors are induced by various inflammatory stimuli. Since myocardial ischaemia-reperfusion results in inflammation, we questioned whether it could induce B1-receptor-dependent responses to des-Arg9-bradykinin (DBK). Thirty-six rabbits were submitted either to a 30 min coronary occlusion followed by a 3 h reperfusion or to a sham operation. The response to DBK was then tested in vivo on mean arterial pressure (MAP) and in vitro on isolated hearts and arterial rings. DBK induced a dose-dependent decrease in MAP in the ischaemia-reperfusion group (DBK, 10 microg kg(-1), intra-arterial: -12 +/- 2 vs. -5 +/- 2 mm Hg in the sham group, P < 0.02), which was significantly antagonised by [Leu8]-des-Arg9-bradykinin (LBK), a B1-receptor antagonist. Following ischaemia-reperfusion, isolated hearts responded to DBK by a decrease in coronary perfusion pressure greater than that of the sham group. DBK dose-dependently decreased the isometric force of isolated carotid rings (DBK, 10(-5) M: -9 +/- 2 vs. -1 +/- 2% in the sham group, P < 0.02) and mesenteric arteries (DBK, 10-6 M: -38 +/- 7% vs. -3 +/- 2 % in the sham group, P < 0.001). The vascular effects of DBK seen after ischaemia-reperfusion were significantly antagonised by LBK. The presence of B1-receptors in ischaemia-reperfusion animals was confirmed by immunolocalisation and Western blot analysis. This study demonstrates that myocardial ischaemia-reperfusion induces a global induction of functional kinin B1-receptors in the endothelium.
Mazenot
C
C
LSCPA, UFR de Pharmacie, Universite Grenoble I, France.
Loufrani
L
L
Henrion
D
D
Ribuot
C
C
Muller-Esterl
W
W
Godin-Ribuot
D
D
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D010477:Perfusion; D011817:Rabbits; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000502:physiology*
D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; C024626:bradykinin, des-Arg(9)-; D001920:Bradykinin