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Pretreatment With Ramiprilat Induces Cardioprotection Against Free Radical Injury In Guinea‐Pig Isolated Heart: Involvement Of Bradykinin, Protein Kinase C And Prostaglandins
Author(s) -
Jin ZhuQiu,
Chen Xiu
Publication year - 2000
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2000.03233.x
Subject(s) - chemistry , cardioprotection , chelerythrine , bradykinin , pharmacology , angiotensin ii , calphostin c , protein kinase c , medicine , biochemistry , receptor , myocardial infarction , kinase
SUMMARY 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 (•O 2 – ), 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 •O 2 – 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 •O 2 – 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 B 2 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 •O 2 – free radical injury. The protective effect depends on activation of B 2 receptors and PKC. Prostaglandin synthesis is also involved.