Protective effect of bradykinin antagonist Hoe-140 during in vivo myocardial ischemic-reperfusion injury in the cat.
The effect of icatibant (Hoe-140), a selective bradykinin receptor (B(2)) antagonist on myocardial ischemic-reperfusion injury was studied in open chest barbiturate anaesthetized cats. The left anterior descending coronary artery was occluded for 15 min, followed by 60 min of reperfusion. Saline or icatibant (200 microg/kg) was administered intravenously slowly over 2 min, 5 min before reperfusion. In the saline-treated group, myocardial ischemic-reperfusion injury was evidenced by depressed MAP, depressed peak positive and negative dP/dt and elevated left ventricular end-diastolic pressure and enhanced oxidative stress [elevated plasma thiobarbituric acid reactive substances (TBARS; a marker for lipid peroxidation), depressed myocardial GSH (reduced glutathione), superoxide dismutase (SOD), catalase] and depletion of adenosine triphosphate (ATP) along with rise in plasma creatine phosphokinase (CPK). Administration of icatibant resulted in complete hemodynamic recovery together with repletion of ATP and reduction in plasma TBARS without any significant change in myocardial SOD, catalase and GSH. The results of the present study suggest a protective role of icatibant in myocardial ischemic-reperfusion injury.
Kumari
Rashmi
R
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110029, India. rashmikumari_s@hotmail.com
Maulik
Mohua
M
Manchanda
Subhash Chandra
SC
Maulik
Subir Kumar
SK
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002415:Cats; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D065168:Bradykinin Receptor Antagonists; D020011:Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; C065679:icatibant; D000255:Adenosine Triphosphate; D001920:Bradykinin