Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin-Converting Enzyme Inhibitors / pharmacology*
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Animals
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Bepridil / analogs & derivatives
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Bepridil / pharmacology
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Biphenyl Compounds
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Bradykinin / analogs & derivatives
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Bradykinin / pharmacology
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Bradykinin Receptor Antagonists
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Cardiovascular Agents / pharmacology
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Cyclooxygenase Inhibitors / pharmacology
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Diastole
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Free Radicals / metabolism
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Free Radicals / pharmacology
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Guinea Pigs
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Heart / drug effects*
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Heart / physiopathology
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Heart Rate / drug effects
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In Vitro Techniques
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Indomethacin / pharmacology
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L-Lactate Dehydrogenase / drug effects
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L-Lactate Dehydrogenase / metabolism
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Male
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Myocardium / metabolism
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Myocardium / pathology
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NG-Nitroarginine Methyl Ester / pharmacology
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Naphthalenes / pharmacology
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Picrates*
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Prostaglandins / metabolism
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism
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Ramipril / analogs & derivatives*
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Ramipril / pharmacology
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Receptors, Bradykinin / physiology
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Thiobarbituric Acid Reactive Substances / metabolism
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Ventricular Function, Left / drug effects
Substances
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Angiotensin-Converting Enzyme Inhibitors
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Biphenyl Compounds
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Bradykinin Receptor Antagonists
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Cardiovascular Agents
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Cyclooxygenase Inhibitors
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Free Radicals
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Naphthalenes
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Picrates
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Prostaglandins
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Receptors, Bradykinin
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Thiobarbituric Acid Reactive Substances
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ramiprilat
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Bepridil
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icatibant
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1,1-diphenyl-2-picrylhydrazyl
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L-Lactate Dehydrogenase
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Protein Kinase C
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calphostin C
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Ramipril
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Bradykinin
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NG-Nitroarginine Methyl Ester
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Indomethacin