Prostacyclin-mediated protection by angiotensin-converting enzyme inhibitors against injury of aortic endothelium by free radicals.
We report here the protective effect of the angiotensin converting enzyme inhibitors captopril and ramiprilat against damage due to oxygen free radicals on aortic endothelium in a superfusion cascade system. Oxygen free radicals were generated by electrolysis of Krebs solution. Acetylcholine was infused through the donor aortic segment and relaxation of the detector aortic ring was used to indicate the release of endothelium-derived relaxing factor (EDRF). The percentage of relaxation before and after electrolysis was compared to calculate the relaxation index. Electrolyzed Krebs solution impaired the release of EDRF, as shown by a reduction in the relaxation index with a concomitant decrease in the tissue levels of superoxide dismutase and 6-keto PGF1 alpha and increase in malondialdehyde in the donor vessel. Captopril (100 microM), 15 microM ramiprilat and 30 nM iloprost had a protective effect as shown by a significantly smaller reduction in the relaxation index and the level of 6-keto PGF1 alpha and by an attenuation of the production of malondialdehyde. In addition, 1 microM indomethacin almost eliminated the protection by captopril. We conclude that both the SH-containing angiotensin-converting enzyme inhibitor captopril and the non-SH-containing ramiprilat, as well as iloprost, a stable analog of prostacyclin, can protect rabbit aortic endothelium against damage due to oxygen free radicals. The mechanism of such protection may be partly associated with the facilitation of the release of prostacyclin and consequent reduction in lipid peroxidation.
Liao
D F
DF
Department of Pharmacology, Hunan Medical University, Changsha, PR China.
Chen
X
X
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D005609:Free Radicals; D016285:Iloprost / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010100:Oxygen / Q000037:antagonists & inhibitors; D011817:Rabbits; D013482:Superoxide Dismutase / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D005609:Free Radicals; D009569:Nitric Oxide; D008315:Malondialdehyde; D015121:6-Ketoprostaglandin F1 alpha; D002216:Captopril; D011464:Epoprostenol; D013482:Superoxide Dismutase; D016285:Iloprost; D010100:Oxygen