Aim: To investigate the mechanism of nickel augmented phenylephrine
(PE)-induced contraction in isolated segments of Wistar rat aorta. Materials and
Methods: Effect of varying concentrations of nickel on PE-induced contraction
were investigated in isolated segments of Wistar rat aorta 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 nickel. Results: Endothelium intact aortic rings incubated with 100
nM, 1 µM or 100 µM of nickel exhibited 80%, 43% and 28% increase in PE-induced
contraction, respectively, while no such enhancing responses were observed in endothelium
denuded aorta. Incubation of aortic rings with 1 µM and 20 µM verapamil suggested an
involvement of influx of calcium through T-type calcium channels in smooth muscle cells,
while aortic rings pre-incubated with gadolinium showed no role of store operated calcium
channels in the nickel effect on PE-induced contractions. The enhancing effect of nickel
on PE-induced contractions was inhibited by apocynin, indomethacin or L-NAME.
Conclusion: Nickel has caused augmentation of PE-induced contractions
as a result of the endothelial generation of reactive oxygen species (ROS) and
cyclooxygenase 2 (COX2) dependent endothelium contracting factors (EDCFs), which increases
the influx of extracellular calcium through T-type Ca2+ channels in smooth
muscle cells.