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 B2-nitric oxide (NO) pathway, prostaglandins(PGs) and protein synthesis in this delayed adaptive response. 2. Rats were pretreated with ramipril (10 or 50 microg 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/dtmax), 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/dtmax, 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 B2 receptor antagonist, NG-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 B2 receptor-NO pathway and depends on protein but not prostaglandin synthesis.
Jin
Z Q
ZQ
Department of Pharmacology, Hunan Medical University, Changsha, P.R. China.
Chen
X
X
D000818:Animals; D005609:Free Radicals / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D015227:Lipid Peroxidation; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011453:Prostaglandins / Q000494:pharmacology; D014176:Protein Biosynthesis; D017257:Ramipril / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors
D005609:Free Radicals; D011453:Prostaglandins; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D017257:Ramipril