Inhibition of sarcolemmal carbon-centered free radical formation by propranolol.
The mechanism of propranolol-inhibited sarcolemmal membrane lipid peroxidation was investigated by electron spin resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and 2-methyl-2-nitrosopropane (MNP). Highly purified canine myocytic sarcolemma were peroxidized by a superoxide-driven (from dihydroxyfumarate) and Fe3+-catalyzed free radical-generating system. Hydroxyl radicals (.OH), identified by electron spin resonance signals as DMPO-OH adducts, were generated in the aqueous phase. Propranolol up to 500 microM did not effectively reduce the intensity of the DMPO-OH adducts. When the sarcolemma were incubated with MNP before the addition of free radicals, MNP adducts characteristic of carbon-centered radicals were produced. Pretreatment of the membranes with propranolol (3-100 microM) decreased the intensity of the MNP adducts in a log concentration-dependent manner; the EC50 is about 7 microM. D- and L-propranolol were found equally effective. When protein-depleted sarcolemmal lipids were similarly incubated with MNP and the free radical system, identical MNP adducts were observed; this finding suggests that the adducts were lipid-derived products arising from lipid peroxidation. Furthermore, their formation was also inhibited by propranolol pretreatment. Since propranolol is not an effective scavenger of oxygen radicals in the aqueous phase, the data suggest that the antiperoxidative effect of propranolol is due to its lipophilic interaction with the membrane and thus subsequent interruption of the free radical chain reactions.
Mak
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Department of Medicine, George Washington University Medical Center, Washington, DC.
Arroyo
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CM
Weglicki
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WB
D000818:Animals; D001696:Biomechanical Phenomena; D002244:Carbon; D055598:Chemical Phenomena; D002621:Chemistry; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011433:Propranolol / Q000494:pharmacology*; D012508:Sarcolemma / Q000378:metabolism*
D005609:Free Radicals; D006878:Hydroxides; D008054:Lipid Peroxides; D017665:Hydroxyl Radical; D002244:Carbon; D011433:Propranolol