Acta Physiologica 2008; Volume 193, Supplement 664
Scandinavian Physiological Society’s Annual Meeting 2008
MITOCHONDRIAL ROS TRIGGERED BY -ADRENERGIC STRESS CONTRIBUTES TO CARDIAC INOTROPY IN WILD-TYPE BUT NOT OB/OB MICE
Abstract number: F0202
ANDERSSON1 DC, FAUCONNIER1 J, KATZ1 A, WESTERBLAD1 H
1Karolinska Institutet, Dept. of physiology and pharmacology, von Eulers Vg 8, 17177 Stockholm, Sweden
We studied if adrenergic stimulation induced production of mitochondrial reactive oxygen species (ROS) in wild type (WT) and obese ob/ob mouse cardiac cells. Also, we studied if ROS affected cardiac Ca2+ transients in adrenergic stimulation.
Freshly isolated ob/ob and WT cardiac cells were paced at 1Hz, cytoplasmic Ca2+ transients ([Ca2+]i) and mitochondrial superoxide were measured in a confocal microscope using fluorescent dyes Fluo-3 and MitoSOX Red, respectively. As a marker of oxidative stress, malondialdehyde (MDA) modification of proteins was detected with western blotting. 100nM isoproterenol (ISO) was used as beta-adrenergic agonist.
ISO increased ROS production in WT cardiac cells. Moreover, WT hearts perfused with ISO for 30 min showed a doubling in MDA relative control. In WT hearts, the amplifying effect of ISO on [Ca2+]i amplitude was diminished in presence of the antioxidant NAC (control: 4.40.32, ISO: 6.60.37, ISO+NAC: 5.20.33); a reduced effect on cell shortening was also seen (increased from 9.81.1 % to 17.91.2 % with ISO and 13.50.9 % with ISO+NAC). In contrast, ob/ob cells did not significantly increase ROS production when exposed to ISO. Control experiments indicated a lower rate of mitochondrial ROS production in ob/ob than WT hearts. The effect of ISO on [Ca2+]i amplitude in ob/ob hearts was not significantly affected by NAC (control: 3.50.22, ISO: 6.00.39, ISO+NAC: 5.60.18).
ROS production in heart contributes to the inotropic effect of beta-adrenergic agonists by increasing the amplitude of [Ca2+]i transients. In contrast to general belief, our data suggest that obesity is associated with decreased ROS production in cardiac muscle.
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Acta Physiologica 2008; Volume 193, Supplement 664 :F0202