Effect on rat arterial blood pressure of chemically generated peroxyl radicals and protection by antioxidants

Abstract

Convincing evidence suggests that blood redox changes play a role in the development of various cardiovascular disorders including hypertension. Nutritional antioxidants have been suggested to play a role in cardiovascular disease prevention. In this study, we investigated in vivo changes in rat arterial blood pressure induced by acute exposition to an increased load of peroxyl radicals and by the administration of selected antioxidants after chemically induced oxidative stress. Hydrosoluble and liposoluble peroxyl radicals, generated by 2,2'-azobis-(2-amidinopropane) dihydrochloride and 2,2'-azobis 2,4-di-methylvaleronitrile, induced a dose-dependent decrease in rat blood pressure. All antioxidants tested (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, vitamin C, glutathione and dithiothreitol) returned peroxyl radical–induced hypotension to normal. Of the various antioxidants tested, glutathione was the most effective in restoring blood pressure after peroxyl radical generation. Treatment of rats with a thiol-chelating agent ( N -ethylmaleimide) and an oxidizing agent (5,5'-dithiobis-2-nitrobenzoic) inhibited peroxyl radical–mediated hypotension. Our results suggest that acute exposition to peroxyl radicals have a hypotensive effect on blood pressure and that thiols play an active role in the redox regulation of blood pressure. Other experiments are needed to clarify the role played by oxidative potentials on blood pressure and the mechanism of action of nutritional antioxidants.