The effect of antioxidant treatment and NOS inhibition on the incidence of ischemia-induced arrhythmias in the diabetic rat heart.
Contrary to clinical trials, experimental studies revealed that diabetes mellitus (DM) may initiate, besides increased myocardial vulnerability to ischemia-reperfusion injury (I/R) and pro/antioxidant dysbalance, development of adaptation leading to an enhanced tolerance to I/R. The aims were to characterize 1) susceptibility to ischemia-induced ventricular arrhythmias in the diabetic rat heart 2) its response to antioxidant N-acetylcysteine (NAC) and a NOS inhibitor L-NAME, and 3) the effect of DM on endogenous antioxidant systems. Seven days after streptozotocin injection (65 mg/kg, i.p.), Langendorff-perfused control (C) and DM hearts were subjected to 30-min occlusion of the LAD coronary artery with or without prior 15-min treatment with L-NAME (100 microM) or NAC (4 mM). Total number of ventricular premature beats (VPB), as well the total duration of ventricular tachycardia (VT) were reduced in the DM group (from 533+/-58 and 37.9+/-10.2 s to 224.3+/-52.6 and 19+/-13.5 s; P<0.05). In contrast to the antiarrhythmic effects of L-NAME and NAC in controls group (VPB 290+/-56 and 74+/-36, respectively; P<0.01 vs. control hearts), application of both drugs in the diabetics did not modify arrhythmogenesis (L-NAME: VPB 345+/-136, VT 25+/-13 s; NAC: VPB 207+/-50, VT 12+/-3.9 s; P>0.05 vs non-treated diabetic hearts). Diabetic state was associated with significantly elevated levels of CoQ10 and CoQ9 (19.6+/-0.8 and 217.3+/-9.5 vs. 17.4+/- 0.5 and 185.0+/-5.0 nmol/g, respectively, in controls; P<0.05), as well as alpha-tocopherol (38.6+/-0.7 vs. 31.5+/-2.1 nmol/g in controls; P<0.01) in the myocardial tissue. It is concluded that early period of DM is associated with enhanced resistance to ischemia-induced arrhythmias. Diabetes mellitus might induce adaptive processes in the myocardium leading to lower susceptibility to antioxidant and L-NAME treatment.
Matejíková
J
J
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Kucharská
J
J
Pancza
D
D
Ravingerová
T
T
D000111:Acetylcysteine / Q000494:pharmacology*; D000222:Adaptation, Physiological; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017180:Tachycardia, Ventricular / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation; D016277:Ventricular Function, Left; D024502:alpha-Tocopherol / Q000378:metabolism
D000975:Antioxidants; D004791:Enzyme Inhibitors; D014451:Ubiquinone; D019001:Nitric Oxide Synthase; C024989:coenzyme Q10; D024502:alpha-Tocopherol; C030571:ubiquinone 9; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine