Ramipril-induced delayed myocardial protection against free radical injury involves bradykinin B2 receptor-NO pathway and protein synthesis

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 mu g 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 TEARS 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 DI 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.