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BioMed Research International
Volume 2014, Article ID 289361, 9 pages
http://dx.doi.org/10.1155/2014/289361
Research Article

Contribution of Ca2+-Dependent Cl Channels to Norepinephrine-Induced Contraction of Femoral Artery Is Replaced by Increasing EDCF Contribution during Ageing

1Institute of Physiology, Academy of Sciences of the Czech Republic, 14220 Prague 4, Czech Republic
2Institute of Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovakia

Received 27 November 2013; Accepted 16 January 2014; Published 23 February 2014

Academic Editor: Iveta Bernatova

Copyright © 2014 Silvia Liskova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The activation of Ca2+-dependent Cl channels during norepinephrine-induced contraction of vascular smooth muscle was suggested to depolarize cell membrane and to increase Ca2+ entry. Hypertension and ageing are associated with altered Ca2+ handling including possible activation of Ca2+-dependent Cl channels. Our study was aimed to determine Ca2+-dependent Cl channels contribution to norepinephrine-induced contraction during hypertension and ageing. Norepinephrine-induced concentration-response curves of femoral arteries from 6- and 12-month-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were recorded using wire myograph. Pretreatment with Ca2+-dependent Cl- channel inhibitor indanyloxyacetic acid 94 [R(+)-IAA-94](IAA) attenuated norepinephrine-induced contraction in all groups, but relatively more in WKY than SHR arteries. The attenuation of norepinephrine-induced contraction after Ca2+-dependent Cl channels blockade was partially reduced in 12-month-old WKY rats, but substantially diminished in 12-month-old SHR. IAA effect was enhanced after NO synthase inhibition but decreased by ageing. In 20-month-old WKY rats norepinephrine-induced contraction was not affected by IAA but was almost abolished after cyclooxygenase inhibition by indomethacin or niflumic acid. In conclusion, contribution of Ca2+-dependent Cl channels to norepinephrine-induced contraction diminished with age, hypertension development, and/or NO synthesis inhibition. Ca2+-dependent Cl channels are important for maintenance of normal vascular tone while their inactivation/closing might be a pathological mechanism.