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SHR Neuro Cancer Cardio Lipid Metab Microb
Heinzel, FR; Luo, Y; Dodoni, G; Boengler, K; Petrat, F; Di Lisa, F; de Groot, H; Schulz, R; Heusch, G.
Formation of reactive oxygen species at increased contraction frequency in rat cardiomyocytes.
Cardiovasc Res. 2006; 71(2):374-382
Doi: 10.1016/j.cardiores.2006.05.014
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- Leading authors Med Uni Graz
- Heinzel Frank
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- Abstract:
- OBJECTIVE: Reactive oxygen species (ROS) play an ambivalent role in cardiomyocytes: low concentrations are involved in cellular signaling, while higher concentrations contribute to cellular injury. We studied ROS formation during increases in contraction frequency in isolated cardiomyocytes. METHODS: Rat ventricular cardiomyocytes were loaded with dichlorodihydrofluorescein and electrically stimulated (37 degrees C). ROS formation was assessed by the rate of oxidation-dependent fluorescence increase (OxR). Oxygen consumption (VO(2)) and NAD(P)H autofluorescence were measured in parallel experiments. RESULTS: Increases in contraction frequency were accompanied by an increase in VO(2) and a decrease in NAD(P)H fluorescence. OxR increased to 124+/-4%, 146+/-8%, 204+/-25% and 256+/-29% of OxR at baseline during 1, 2, 3 and 4 Hz stimulation, and subsequently returned to baseline values with 0.2 Hz. The OxR increase was dose-dependently inhibited by the antioxidant NAC (10 and 100 mM), but unaffected by the NO synthase inhibitor l-NAME (200 microM and 10 mM). The OxR increase was attenuated when myosin ATPase activity was inhibited by butanedione monoxime (BDM; 5 mM). CONCLUSION: Increased contraction frequency induces ROS formation in rat cardiomyocytes.
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