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.

Institute of Pharmacology Faculty of Medicine Comenius University Bratislava Slovakia

Institute of Physiology Academy of Sciences of the Czech Republic 14220 Prague 4 Czech Republic

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

Biomed Res Int. 2018 Feb 20;2018:3081532. doi: 10.1155/2018/3081532. PubMed

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