BRADYKININ IMPROVES POSTISCHEMIC RECOVERY IN THE RAT-HEART - ROLE OF HIGH-ENERGY PHOSPHATES, NITRIC-OXIDE, AND PROSTACYCLIN

Objective: The aim was to define: (1) whether bradykinin administratio n during reperfusion improves postischaemic myocardial recovery; (2) w hether high energy phosphate compounds are involved in the protective effects of bradykinin; and (3) whether bradykinin-induced release of p rostacyclin and nitric oxide mediate the protective effects of bradyki nin. Methods: In the Langendorff rat heart preparation, coronary flow, left ventricular developed pressure, and, using P-31 magnetic resonan ce spectroscopy, the high energy phosphate compounds phosphocreatine a nd beta-ATP were assessed during 15 min of global ischaemia and 30 min of reperfusion. Administration of 10(-7) M bradykinin was started bef ore 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 ind omethacin (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 pressur e [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, recover y of coronary flow [71(4)% v 43(4)%, P < 0.05] and left ventricular pr essure [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 star ting 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 heart s are dependent from an unrestrained action of prostacyclin and nitric oxide.