Pretreatment With Ramiprilat Induces Cardioprotection Against Free Radical Injury In Guinea‐Pig Isolated Heart: Involvement Of Bradykinin, Protein Kinase C And Prostaglandins

Abstract

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 (•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.