Antioxidant properties of dihydropyridines in isolated rat hearts.
Isolated Sprague-Dawley rat hearts were perfused under constant flow conditions. Hearts were treated with vehicle or treatment buffers, including nisoldipine, nifedipine, or the optical isomers (+)- or (-)-nisoldipine. H2O2 (500-600 microM) was then added to the treatment buffer for 12 min. H2O2 was removed and perfusion continued with treatment buffers (10 min) followed by control buffer (20 min). Contractile function decreased following perfusion with H2O2. Contractile function was protected was protected in a concentration-dependent manner (nisoldipine=19,26,50,63 and 78%; nifedipine = 23, 37, 55,61, and 63% of pre-peroxide function, 0, 0.1, 0.5 1.0, and 5 microliter, respectively). There were no significant differences between equal concentrations of nisoldipine and nifedipine. Contractile function was equally protected by both (+)- and (-)-nisoldipine compared with vehicle-treated hearts (56, 67, and 16%, of pre-peroxide function, respectively). Biochemical analyses indicated that H2O2 damaged plasma membranes (increased lactate dehydrogenase leak) and caused lipid peroxidation (elevated tissue thiobarbituric acid reactive substances). Biochemical changes were equally reduced by nisoldipine and nifedipine treatments and by (+)- and (-)-nisoldipine. The treatment groups have widely differing IC50 values as calcium channel antagonists, yet they had equal effects in reducing oxidative injury, suggesting that this beneficial effect is not mediated by calcium antagonism.
Kauder
W F
WF
Department of Biology, University of North Carolina at Charlotte, 28223, USA.
Watts
J A
JA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy*; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D015737:Nisoldipine / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013997:Time Factors
D000975:Antioxidants; D002121:Calcium Channel Blockers; D015737:Nisoldipine; D006861:Hydrogen Peroxide; D009543:Nifedipine