Vasodilatory and toxic effects of spin traps on aerobic cardiac function.
The objective of this study was to compare the effect of several structurally related nitrone and nitroso spin traps on the function of the isolated bicarbonate-buffer perfused rat heart model. Spin traps investigated were alpha-phenyl-tert-butyl N-nitrone (PBN), alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (POBN), 2-methyl-2-nitroso propane (MNP), 2-hydroxymethyl-2-nitroso propane (MNP/OH), nitrosobenzene (NB), dibromonitrosobenzene-sulfonic acid (DBNBS), and 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO). During perfusion of hearts with increasing concentrations of spin traps, ventricular pressure, coronary flow rate, and heart rate were continuously recorded. The extent of contractile recovery was subsequently measured upon return to spin-trap free perfusion. The percentage of maximum increase in coronary flow with PBN, POBN, MNP, MNP-OH, NB, DBNBS, and DMPO were 11, 40, 45, 66, 28, 28, and 29%, respectively. Thus, all nitroso and nitrone spin traps studied acted as vasodilators. Over the dose range studied, POBN, MNP, MNP/OH, and DMPO did not exert any chronotropic effect. PBN, NB, and DBNBS exerted a negative chronotropic effect at higher concentrations. All spin traps studied, with the exception of DMPO, exerted a negative inotropic effect at the higher concentrations studied. We conclude that all spin traps examined acted as coronary vasodilators. Their negative chronotropic and inotropic effects were minimal in comparison and only manifest at the higher concentrations studied.
Konorev
E A
EA
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226.
Baker
J E
JE
Joseph
J
J
Kalyanaraman
B
B
D000332:Aerobiosis; D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003497:Cyclic N-Oxides; D003864:Depression, Chemical; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D008353:Mannitol / Q000494:pharmacology; D009589:Nitrogen Oxides / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010477:Perfusion; D011312:Pressure; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D014664:Vasodilation / Q000187:drug effects*; D016276:Ventricular Function
D001557:Benzenesulfonates; D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D009603:Nitroso Compounds; D011725:Pyridines; D013113:Spin Labels; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; C029217:phenyl-N-tert-butylnitrone; D008353:Mannitol; C048757:3,5-dibromo-4-nitrosobenzenesulfonate; C034526:tert-nitrosobutane; C012456:nitrosobenzene