icatibant and 1-1-diphenyl-2-picrylhydrazyl

1. Pretreatment with ramiprilat, an angiotensin-converting enzyme (ACE) inhibitor, induced cardioprotection and its possible mechanism of action was investigated in guinea-pig Langendorff perfused heart. 2. Superoxide anion (*O2-), produced by hypoxanthine and xanthine oxidase, and the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical were used for triggering free radical injury in cardiac tissue. 3. 1,1-Diphenyl-2-picryl-hydrazyl and *O2- significantly reduced left ventricular developed pressure (LVDP), +/-dP/dt(max), heart rate and coronary flow. Left ventricular end-diastolic pressure (LVEDP) was elevated and lactate dehydrogenase (LDH) leakage and the formation of thiobarbituric acid-reactive substances (TBARS) formation were significantly increased. 4. Pretreatment with ramiprilat induced cardioprotection against DPPH and *O2- free radical injury. Cardiac functions (LVDP, LVEDP and +/-dP/dt(max)) were significantly improved. Both LDH and TBARS were reduced. 5. HOE 140 (a selective bradykinin B2 receptor antagonist), calphostin C (a protein kinase C (PKC) inhibitor) and indomethacin (a cyclo-oxygenase inhibitor) all abolished the cardiac protective effect of ramiprilat. However, N(G)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, had no effect. 6. In conclusion, ramiprilat pretreatment induces cardioprotection against either DPPH or *O2- free radical injury. The protective effect depends on activation of B2 receptors and PKC. Prostaglandin synthesis is also involved.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bepridil; Biphenyl Compounds; Bradykinin; Bradykinin Receptor Antagonists; Cardiovascular Agents; Cyclooxygenase Inhibitors; Diastole; Free Radicals; Guinea Pigs; Heart; Heart Rate; In Vitro Techniques; Indomethacin; L-Lactate Dehydrogenase; Male; Myocardium; Naphthalenes; NG-Nitroarginine Methyl Ester; Picrates; Prostaglandins; Protein Kinase C; Ramipril; Receptors, Bradykinin; Thiobarbituric Acid Reactive Substances; Ventricular Function, Left

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.

Topics: Adrenergic beta-Antagonists; Animals; Bepridil; Biphenyl Compounds; Bradykinin; Bradykinin Receptor Antagonists; Free Radicals; Guinea Pigs; Heart Rate; In Vitro Techniques; Indicators and Reagents; Ischemic Preconditioning, Myocardial; Male; Myocardium; Picrates; Receptor, Bradykinin B2; Thiobarbituric Acid Reactive Substances; Ventricular Function, Left