Differential effects of superoxide radical on the action potentials in ventricular muscles, Purkinje fibers and atrial muscles in the heart of different aged rats.
The purpose of this study was to determine whether the effects of the superoxide donor menadione on myocardial electrical activity were regional and/or age-dependent. Action potentials were recorded in cardiac muscles that were isolated from 18- and 49-day old rat hearts, using a conventional microelectrode technique. Superoxide dismutase (SOD) activity was determined spectrophotometrically in regional cardiac muscles. Menadione (30 microM) significantly increased the action potential duration at 90% repolarization (APD90) in Purkinje fibers and ventricular muscles from 18-day old rats; and it decreased the APD in ventricular muscles from 49-day old rats. ATP-sensitive K+ (KATP) channel opener pinacidil blocked menadione-induced effects on the APD90 of Purkinje fibers and ventricular muscles from 18-day old rats, but did not block menadione-induced effects on the APD90 of Purkinje fibers and ventricular muscles from 49-day old rats. The cGMP-dependent protein kinase (PKG) activator or inhibitor did not inhibit the menadione-induced effects on APD90 of ventricular muscles and Purkinje fibers from 18- and 49-day old rats. The superoxide dismutase (SOD) activities in ventricular muscles from 4-, 18- and 49-day old rats, were: 1185 +/- 135, 1434 +/- 96, and 1760 +/- 144 U/mg protein, respectively; whereas, the SOD activities in atrial muscles, were: 1135.4 +/- 156.4, 1145.4 +/- 148.8, and 1243.5 +/- 175.2 U/mg protein, respectively. However, the ventricular SOD activities were significantly inhibited under hypoxic conditions. These results indicate that menadione can produce regionally differential effects on cardiac APD, which may be due to differences in the SOD activity, depending on the region and age of the cardiac tissue.
Ha
Ki-Chan
KC
Department of Pharmacology, Chonbuk National University Medical School, Jeonju, 560-182, Korea.
Kwak
Yong-Guen
YG
Piao
Cheng-Shil
CS
Chae
Han-Jung
HJ
Chae
Soo-Wan
SW
D000200:Action Potentials / Q000187:drug effects*; D000367:Age Factors; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D024483:Vitamin K 3 / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D013481:Superoxides; C016276:8-bromocyclic GMP; D024483:Vitamin K 3; D020110:Pinacidil; D013482:Superoxide Dismutase; D006152:Cyclic GMP