To investigate the mechanism of cobalt-mediated phenylephrine (PE)-induced contraction in endothelium-intact isolated Wistar rat aortic rings. Effect of dose-dependent concentrations of cobalt on PE-induced contraction was investigated in isolated Wistar rat aortic rings using an organ bath system. Aortic rings were pre-incubated with verapamil (1 μM and 20 μM), gadolinium, apocynin, indomethacin or N-G-nitro-l-arginine methyl ester (L-NAME) separately before incubation with cobalt. Endothelium-intact aortic rings were incubated with 800 nM, 1 μM, 10 μM, 50 μM cobalt; we observed 20%, 22%, 32% and 27% increased contractions respectively, while no effect was seen in tension recording on cobalt exposure. Incubation of endothelium-intact aortic rings with 100 μM apocynin and 100 μM L-NAME suggested the role of NADPH oxidase in generation of reactive oxygen species (ROS) and decrease in bioavailability of nitric oxide (NO) from eNOS on exposure to cobalt. Aortic rings pre-incubated with 1 μM and 20 μM verapamil suggested role of both L-type and T-type calcium channels in influx of extracellular calcium in smooth muscle cells. We observed no role of store-operated calcium channels (SOCC) in calcium influx due to cobalt exposure and cyclooxygenase in generation of prostanoids in isolated aortic rings. Cobalt caused rise of PE-induced contractions as a result of the endothelial generation of ROS, by decreasing bioavailability of NO. Generation of ROS may be responsible for causing the influx of extracellular calcium through L-type and T-type Ca2+ channels in smooth muscle cells.
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Wani, S.A., Khan, L.A. & Basir, S.F. Cobalt-Induced Hypercontraction is Mediated by Generationof Reactive Oxygen Species and Influx of Calcium in Isolated RatAorta. Biol Trace Elem Res 196, 110–118 (2020). https://doi.org/10.1007/s12011-019-01890-5
- Reactive oxygen species
- Calcium channels
- Nitric oxide