Contribution of Ca²⁺-dependent Cl⁻ channels to norepinephrine-induced contraction of femoral artery is replaced by increasing EDCF contribution during ageing.
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 Physiology, Academy of Sciences of the Czech Republic, 14220 Prague 4, Czech Republic ; Institute of Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
Silvia
S
Liskova
Institute of Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
Miriam
M
Petrova
Institute of Physiology, Academy of Sciences of the Czech Republic, 14220 Prague 4, Czech Republic.
Petr
P
Karen
Institute of Physiology, Academy of Sciences of the Czech Republic, 14220 Prague 4, Czech Republic.
Michal
M
Behuliak
Institute of Physiology, Academy of Sciences of the Czech Republic, 14220 Prague 4, Czech Republic.
Josef
J
Zicha
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism*; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D006973:Hypertension / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009589:Nitrogen Oxides / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D018118:Chloride Channels; D016232:Endothelins; D009589:Nitrogen Oxides; D002118:Calcium; D009638:Norepinephrine