Contribution of Ca2+-Dependent Cl− Channels to Norepinephrine-Induced Contraction of Femoral Artery Is Replaced by Increasing EDCF Contribution during Ageing. (23rd February 2014)

• Record Type: Journal Article
• Authors: Liskova, Silvia; Petrova, Miriam; Karen, Petr; Behuliak, Michal; Zicha, Josef
• Other Names: Bernatova Iveta Academic Editor.
• Is Part Of: BioMed research international. Volume 2014(2014)
• Publication Date: 2014-02-23
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2014/289361
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : The activation of Ca 2+ -dependent Cl − channels during norepinephrine-induced contraction of vascular smooth muscle was suggested to depolarize cell membrane and to increase Ca 2+ entry. Hypertension and ageing are associated with altered Ca 2+ handling including possible activation of Ca 2+ -dependent Cl − channels. Our study was aimed to determine Ca 2+ -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 Ca 2+ -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 Ca 2+ -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 Ca 2+ -dependent Cl − channels to norepinephrine-induced contraction diminished with age, hypertension development, and/or NO synthesis inhibition. Ca 2+ -dependent Cl − channels are important for maintenance of normal vascular tone while their inactivation/closing might be a pathological mechanism.