Dose-Dependent Differential Effects of In Vivo Exposure of Cadmium on Myometrial Activity in Rats: Involvement of VDCC and Ca2+-Mimicking Pathways
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Present study was undertaken to study the effect of 28-days exposure of female adult rats to cadmium (Cd) in drinking water @ 3, 10 and 30 parts per million (ppm) on myometrial responsiveness to different spasmogens and unravel the possible mechanism of alterations in myometrial activity. Cadmium and Ca2+ levels in blood and uterus were measured by atomic absorption spectroscopy while isometric tension in myometrial strips was measured using data acquisition system-based physiograph. Dose-dependent increase in levels of cadmium was observed in both blood and uterus while calcium was increased only in the uterus as compared to those in control. Significant increase in absolute tension and mean integral tension along with non-significant increase in frequency of myometrial contraction was observed in rats of Cd-treated groups. As compared to the control, cadmium decreased and increased the effects of calcium chloride, 80 mM KCl, histamine (0.1 μM) and oxytocin (10−2 IU/ml) in lower-dose (3 ppm) and higher-dose groups (10 and 30 ppm), respectively. Cadmium potentiated and inhibited the relaxant response to phenylephrine in myometrium of rats at lower-dose (3 ppm) and highest-dose (30 ppm) Cd-treated groups, respectively. Results of our study revealed that Cd accumulates in the myometrium of rats and alters its responsiveness to oxytocin, histamine, 80 mM KCl, calcium chloride and phenylephrine, and these effects are differentially mediated depending on levels of exposure possibly through voltage-dependent calcium channel (VDCC) and Ca2+-mimicking pathways.
KeywordsCadmium Myometrium VDCC Calcium Phenylephrine
This work was supported by the Indian Council of Agriculture Research (ICAR), New Delhi, under Niche Area of Excellence programme to the Department of Veterinary Pharmacology and Toxicology, DUVASU, Mathura, India (Grant No:10(10)/2012-EPD, dated: 23rd March, 2012).
Compliance with Ethical Standards
All the experimental studies were undertaken after approval of the Institutional Animal Ethics Committee, DUVASU, Mathura, as per the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA).
Conflict of Interest
The authors declare that they have no competing interests.
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