Antioxidant or pro-oxidant properties of epinephrine (EPI) and isoprenaline (ISO) were studied in the absence and presence of Fe2+ , Fe3+ and Cu2+ ions. EPI and ISO (>2 /tmol/1) inhibited peroxidation of low density lipoprotein (LDL) induced by 2, 2’-azobis(2-amidino-propane) (AAPH). EPI had a similar inhibitory potency as ISO, but their potency was several times higher than the potency of a-tocopherol (a-TOC). When the LDL peroxidation was induced by 5 /tmol/1 CUSO4, EPI and ISO enhanced LDL peroxidation at low concentrations (10/mol/l) and decreased peroxidation at higher concentrations (30 /tmol/1). The compounds had a similar tendency to inhibit the peroxidation of phosphatidylcholine liposomes. EPI (3-30 //¿mol/1) inhibited lipid peroxidation of phosphatidylcholine liposomes induced by 2 mmol/1 of AAPH, but it was less effective and even increased the peroxidation, when the samples contained 2 mmol/1 AAPH with 50 /¿mol/l FeSC>4 or 2 mmol/1 AAPH with 20/imol/l FeCb. Inhibition of lipid peroxidation by EPI was also observed when studying decreased oxygen consumption, when the peroxidation of linoleic acid was induced by lipoxidase. In conclusion, EPI and ISO reduced lipid peroxidation, but they exhibit pro-oxidant properties in the presence of Fe2+, Fe3+ or Cu2+ ions, depending on the catecholamine and ionic concentration.
Five potential /3-adrenoceptor blocking (BAB) compounds, alkylesters of 4-[(2-hydroxy-3-alkylamino)propoxy] phenylcarbamic acid, and eight calcium channel blockers (CB), i.e. nifedipine, nimodipine, niludipine, nitrendipine, verapamil, gallopamil, mepamil and diltiazem, were compared as to their inhibitory effect on thrombin induced aggregation of washed rat platelets and their effect on dynamies/disorder of liposomal membranes prepared from platelet lipids, studied by EPR spectroscopy of a lipid spin probe. The anti-aggregatory potency of the BAB and CB drugs was effective within the concentration range of 0.01-1 mmol/1. The antiaggregatory potency of BAB increased in the order BL- 143< BL-243< BL-343 < BL-443 < BL-543 and among the CB, nifedipine and diltiazem were the least potent, whereas nitrendipine and mepamil were the most potent drugs. The potency of the other CB tested was intermediate. The BAB drugs increased the dynamies/disorder of the liposomes in the same order as they inhibited platelet aggregation, whereas there was no relationship between antiaggregatory effect of CB and their influence on dynamies/disorder of the liposomes. Nifedipine, nimodipine, niludipine and nitrendipine had a minor perturbation effect on the liposomes, whereas verapamil, mepamil, gallopamil and diltiazem pronouncedly increased the dynamies/disorder of the hydro- phobic part of the liposomes. The results indicate that the anti-aggregatory activity of BAB drugs may be mediated, at least partially, through their perturbation effect on the lipid part of biological membranes.