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 3'P magnetic resonance
... c resonance spectroscopy, the high energy phosphate compounds phosphocreatine and B-ATP were assessed during 15 min of global ischaemia and 30 min of reperfusion. Administration of 10m7 M bradykinin was started before ischaemia and maintained throughout the experiment (BK-pre). This was compared to 10e7 M bradykinin given exclusively with reperfusion (BK-post). Then 10e7 M bradykinin was given simultaneously with lOi' M Nw-nitro-L-arginine-methyl ester (BK-LNAME) or 10m5 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 < 0.051, left ventricular pressure [81(S)% v 42(5)%, P< 0.051, phosphocreatine [105(4)% v 67(g)%, P <0.05], and B-ATP [78(9)% v 48(7)%, P<O.O5]. With BK-post, recovery of coronary flow [71(4)% v 43(4)%, P<O.O5] and left ventricular pressure [78(4)% v 42(5)%, P < 0.051 significantly improved; however the recovery of phosphocreatine [70(4)% v 67(g)%, NS] and B-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.