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Bitter tastants induce relaxation of rat thoracic aorta precontracted with high K +
Author(s) -
Sai WenBo,
Yu MengFei,
Wei MingYu,
Lu Zhongju,
Zheng YunMin,
Wang YongXiao,
Qin Gangjian,
Guo Donglin,
Ji Guangju,
Shen Jinhua,
Liu QingHua
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12217
Subject(s) - nifedipine , myograph , thoracic aorta , glibenclamide , chemistry , calcium , medicine , voltage dependent calcium channel , extracellular , patch clamp , channel blocker , aorta , anatomy , endocrinology , anesthesia , contraction (grammar) , receptor , biochemistry , diabetes mellitus
Summary It has been reported that bitter tastants decrease blood pressure and relax precontracted vascular smooth muscle. However, the underlying mechanisms remain unclear. The aim of the present study was to determine the mechanism underlying the vasorelaxant effect of the bitter tastants. Thoracic aortic rings were isolated from Wistar rats and contractions were measured using an isometric myograph. Intracellular Ca 2+ ([Ca 2+ ] i ) in single rat thoracic aortic smooth muscle cells was recorded by calcium imaging. Calcium currents in single cells were recorded using patch‐clamp techniques. High K + (140 mmol/L) induced contractions in rat thoracic aortic rings that were inhibited by 3 mmol/L chloroquine, 3 mmol/L denatonium and 10 μ mol/L nifedipine. In single rat thoracic aortic smooth muscle cells, high K + increased [Ca 2+ ] i and this effect was also blocked by 3 mmol/L chloroquine and 10 μ mol/L nifedipine. Under Ca 2+ ‐free conditions, high K + failed to induce contractions in rat thoracic aortic rings. On its own, chloroquine had no effect on the muscle tension of rat aortic rings and [Ca 2+ ] i . The vasorelaxant effects of chloroquine on precontracted rat thoracic aortic rings were not altered by either 1 μ g/mL pertussis toxin (PTX), an inhibitor of G α o/i ‐protein, or 1 mmol/L gallein, an inhibitor of G βγ ‐protein. The results of patch‐clamp analysis in single cells indicate that 1 mmol/L chloroquine blocks voltage‐dependent L‐type Ca 2+ channel (VDLCC) currents from both extracellular and intracellular sides. Together, the results indicate that chloroquine can block VDLCC, independent of PTX‐ and gallein‐sensitive G‐proteins, resulting in relaxation of high K + ‐precontracted thoracic aortic smooth muscle.