Induces vasodilatation of rat mesenteric artery in vitro mainly by inhibiting receptor-mediated Ca(2+)-influx and Ca(2+)-release.
The purpose of this study was to investigate the effect of atropine on peripheral vasodilation and the mechanisms involved. The isometric tension of rat mesenteric artery rings was recorded in vitro on a myograph. The results showed that atropine, at concentrations greater than 1 microM, relaxed the noradrenalin (NA)-precontracted rat mesenteric artery in a concentration-dependent manner. Atropine-induced vasodilatation was mediated, in part, by an endothelium-dependent mechanism, to which endothelium-derived hyperpolarizing factor may contribute. Atropine was able to shift the NA-induced concentration-response curve to the right, in a non-parallel manner, suggesting the mechanism of atropine was not mediated via the (alpha1-adrenoreceptor. The beta-adrenoreceptor and ATP sensitive potassium channel, a voltage dependent calcium channel, were not involved in the vasodilatation. However, atropine inhibited the contraction derived from NA and CaCI2 in Ca(2+)-free medium, in a concentration dependent manner, indicating the vasodilatation was related to the inhibition of extracellular Ca2+ influx through the receptor-operated calcium channels and intracellular Ca2+ release from the Ca2+ store. Atropine had no effect on the caffeine-induced contraction in the artery segments, indicating the inhibition of intracellular Ca2+ release as a result of atropine most likely occurs via the IP3 pathway rather than the ryanodine receptors. Our results suggest that atropine-induced vasodilatation is mainly from artery smooth muscle cells due to inhibition of the receptor-mediated Ca(2+)-influx and Ca(2+)-release, and partly from the endothelium mediated by EDHF.
Cao
Yong-Xiao
YX
Department of Pharmacology, Medical School of Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi Province 710061, P. R. China. yxy@xjtu.edu.cn
Zheng
Jian-Pu
JP
He
Jian-Yu
JY
Li
Jie
J
Xu
Cang-Bao
CB
Edvinsson
Lars
L
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002110:Caffeine; D002118:Calcium / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002122:Calcium Chloride / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007213:Indomethacin; D017136:Ion Transport / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D012701:Serotonin; D002110:Caffeine; D011189:Potassium Chloride; D001285:Atropine; D002122:Calcium Chloride; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin