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  • Title: Bradykinin improves postischaemic recovery in the rat heart: role of high energy phosphates, nitric oxide, and prostacyclin.
    Author: Zhu P, Zaugg CE, Simper D, Hornstein P, Allegrini PR, Buser PT.
    Journal: Cardiovasc Res; 1995 May; 29(5):658-63. PubMed ID: 7606754.
    Abstract:
    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.
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