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Ramipril‐induced delayed myocardial protection against free radical injury involves bradykinin B 2 receptor‐NO pathway and protein synthesis
Author(s) -
Jin ZhuQiu,
Chen Xiu
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702089
Subject(s) - bradykinin , ramipril , icatibant , chemistry , nitric oxide synthase , bradykinin receptor , tbars , pharmacology , medicine , endocrinology , cyclooxygenase , receptor antagonist , nitric oxide , receptor , antagonist , biochemistry , enzyme , blood pressure , lipid peroxidation
1 The aim of the present study was to examine whether ramipril induces delayed myocardial protection against free radical injuries ex vivo and to determine the possible role of the bradykinin B 2 –nitric oxide (NO) pathway, prostaglandins(PGs) and protein synthesis in this delayed adaptive response. 2 Rats were pretreated with ramipril (10 or 50 μg kg −1 , i.v.) and hearts were isolated after 24, 48 and 72 h. Langendorff hearts were subjected to 1,1‐diphenyl‐2‐picryl‐hydrazyl (DPPH) free radical‐induced injury. 3 Left ventricular developed pressure (LVDP) and its maximal increase velocity (+dP/dt max ), coronary flow (CF), heart rate (HR), lactate dehydrogenase (LDH) in coronary effluent and thiobarbituric acid reactive substances (TBARS) in the myocardium were measured. 4 The results showed that in the DPPH control group, 20 min after free radical‐induced injury, LVDP, +dP/dt max , CF, HR declined, whereas TBARS and LDH increased significantly. The above cardiac function parameters were significantly improved in RAM‐pretreated rats after 24 and 48 h. 5 Pretreatment with HOE 140, the selective bradykinin B 2 receptor antagonist, N G ‐nitro‐ L ‐arginine, the NO synthase inhibitor, and actinomycin D, the RNA transcription inhibitor, prior to ramipril injection abolished the beneficial effects of ramipril at 24 h while indomethacin, a cyclooxygenase inhibitor, pretreatment had no effect on ramipril‐induced delayed protection. 6 In conclusion, ramipril induces delayed myocardial protection against free radical injury in the rat heart. This delayed protection was sustained for 48 h, is associated with the bradykinin B 2 receptor–NO pathway and depends on protein but not prostaglandin synthesis.British Journal of Pharmacology (1998) 125 , 556–562; doi: 10.1038/sj.bjp.0702089