Bradykinin improves postischaemic recovery in the rat heart: role of high energy phosphates, nitric oxide, and prostacyclin.
OBJECTIVE
The aim was to define: (1) whether bradykinin administration during reperfusion improves postischaemic myocardial recovery; (2) whether high energy phosphate compounds are involved in the protective effects of bradykinin; and (3) whether bradykinin-induced release of prostacyclin and nitric oxide mediate the protective effects of bradykinin.


METHODS
In the Langendorff rat heart preparation, coronary flow, left ventricular developed pressure, and, using 31P magnetic resonance spectroscopy, the high energy phosphate compounds phosphocreatine and beta-ATP were assessed during 15 min of global ischaemia and 30 min of reperfusion. Administration of 10(-7) M bradykinin was started before ischaemia and maintained throughout the experiment (BK-pre). This was compared to 10(-7) M bradykinin given exclusively with reperfusion (BK-post). Then 10(-7) M bradykinin was given simultaneously with 10(-4) M N omega-nitro-L-arginine-methyl ester (BK-LNAME) or 10(-5) M indomethacin (BK-indo).


RESULTS
In comparison to control hearts, BK-pre exerted a significant protective effect on the postischaemic recovery of coronary flow [71(5)% v 43(4)%, P < 0.05], left ventricular pressure [81(8)% v 42(5)%, P < 0.05], phosphocreatine [105(4)% v 67(8)%, P < 0.05], and beta-ATP [78(9)% v 48(7)%, P < 0.05]. With BK-post, recovery of coronary flow [71(4)% v 43(4)%, P < 0.05] and left ventricular pressure [78(4)% v 42(5)%, P < 0.05] significantly improved; however the recovery of phosphocreatine [70(4)% v 67(8)%, NS] and beta-ATP [58(2)% v 48(7)%, NS] was not different from control. When bradykinin and L-NAME or indomethacin was given the beneficial effects of bradykinin on ischaemic hearts were abolished.


CONCLUSIONS
(1) Bradykinin improved postischaemic myocardial recovery when given before ischaemia or starting exclusively with reperfusion; (2) this was only partially related to a protective action on the high energy phosphate compounds during ischaemia; (3) the beneficial effects of bradykinin on ischaemic hearts are dependent from an unrestrained action of prostacyclin and nitric oxide.
Zhu
P
P
Division of Cardiology, DIM, University Hospital, Basel, Switzerland.
Zaugg
C E
CE
Simper
D
D
Hornstein
P
P
Allegrini
P R
PR
Buser
P T
PT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000627:therapeutic use*; D011464:Epoprostenol / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D010725:Phosphocreatine; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D011464:Epoprostenol; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin