Detrimental implication of B1 receptors in myocardial ischemia: evidence from pharmacological blockade and gene knockout mice.
OBJECTIVE
The aim of this study was to evaluate the contribution of kinin B1 receptors in myocardial ischemia using both pharmacological blockade and gene knockout mice.


METHODS
Hearts (n = 6-8 per group) from wild type or homozygous B1 receptor gene knockout mice were isolated and perfused using the Langendorff technique. After a 30-min stabilisation period, the left coronary artery was occluded for 30 min followed by 60 min of reperfusion. In two separate groups of wild type hearts, B1 and B2 receptors were blocked with 3 nM of (des-Arg9, Leu8)-bradykinin and 10 nM of Hoe 140, respectively, (started 15 min before ischemia and stopped before the reperfusion).


RESULTS
Infarct size to risk zone (I/R) ratio was significantly reduced in hearts of knockout mice (11.3 +/- 2.1%) compared to those of wild type mice (25.7 +/- 1.7%). Furthermore, in wild type mice, I/R was significantly reduced in hearts perfused with the B1 receptor antagonist (12.8 +/- 2.4%) but not in hearts perfused with the B2 receptor antagonist (36.3 +/- 4.4%) compared to untreated hearts. Finally, a RT-PCR technique showed an activation of kinin B1 receptor gene transcription, in wild type hearts, subjected to the ischemia-reperfusion sequence.


CONCLUSIONS
This study demonstrates that B1 receptors are induced during myocardial ischemia where they could play a detrimental role in mice.
Lagneux
Caroline
C
Laboratoire du Stress Cardiovasculaire et Pathologies Associées, Université Joseph Fourier, La Tronche, France. caroline.lagneux@staff.mcgill.ca
Bader
Michael
M
Pesquero
João B
JB
Demenge
Pierre
P
Ribuot
Christophe
C
D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D065168:Bradykinin Receptor Antagonists; D005260:Female; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009929:Organ Size / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D065168:Bradykinin Receptor Antagonists; D012333:RNA, Messenger; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin