Bradykinin mediates myocardial ischaemic preconditioning against free radical injury in guinea-pig isolated heart.
1. Myocardial ischaemic preconditioning (IP) against free radical injury and its possible mediator(s) was investigated in a Langendorff-perfused guinea-pig heart. 2. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) was used for triggering free radical injury in cardiac tissue. It reduced left ventricular developed pressure (LVDP), +/- dp/dtmax, heart rate (HR) and coronary flow (CF) and increased thiobarbituric acid-reactive substances (TBARS) in cardiac tissue. 3. Ischaemic preconditioning (5 min global ischaemia and 5 min reperfusion) exerted cardioprotection against DPPH-induced functional impairment, with significant improvement in LVDP, +/- dp/dtmax, HR and CF. The formation of TBARS in cardiac tissue was reduced. Blockade of bradykinin (BK) B2 receptors with icatibant (HOE 140) abolished the cardio-protective effects of IP. 4. Bradykinin (10(-7) mol/L) perfusion for 10 min protected the heart against free radical injury. The cardioprotection induced by BK was reversed by HOE 140. 5. Pretreatment with IP and BK results in cardiac protection against free radical injury through the activation of B2 receptors. Endogenously generated BK may mediate IP in the guinea-pig heart.
Jin
Z Q
ZQ
Department of Pharmacology, Hunan Medical University, Changsha, China.
Chen
X
X
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015764:Bepridil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D001713:Biphenyl Compounds; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use*; D065168:Bradykinin Receptor Antagonists; D005609:Free Radicals / Q000378:metabolism / Q000633:toxicity; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007202:Indicators and Reagents / Q000378:metabolism / Q000633:toxicity*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010851:Picrates; D043782:Receptor, Bradykinin B2; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D001713:Biphenyl Compounds; D065168:Bradykinin Receptor Antagonists; D005609:Free Radicals; D007202:Indicators and Reagents; D010851:Picrates; D043782:Receptor, Bradykinin B2; D017392:Thiobarbituric Acid Reactive Substances; D015764:Bepridil; C065679:icatibant; C004931:1,1-diphenyl-2-picrylhydrazyl; D001920:Bradykinin