Bitter tastants induce relaxation of rat thoracic aorta precontracted with high K
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...
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Published in | Clinical and experimental pharmacology & physiology Vol. 41; no. 4; pp. 301 - 308 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Australia
Blackwell Publishing Ltd
01.04.2014
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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 Ca2+ ([Ca2+]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 μmol/L nifedipine. In single rat thoracic aortic smooth muscle cells, high K+ increased [Ca2+]i and this effect was also blocked by 3 mmol/L chloroquine and 10 μmol/L nifedipine. Under Ca2+‐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 [Ca2+]i. The vasorelaxant effects of chloroquine on precontracted rat thoracic aortic rings were not altered by either 1 μg/mL pertussis toxin (PTX), an inhibitor of Gαo/i ‐protein, or 1 mmol/L gallein, an inhibitor of Gβγ‐protein. The results of patch‐clamp analysis in single cells indicate that 1 mmol/L chloroquine blocks voltage‐dependent L‐type Ca2+ 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. |
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Bibliography: | National Natural Science Foundation of China - No. 31140087; No. 30971514 Figure S1. High K+-induced precontraction in rat thoracic aortic rings is inhibited by denatonium.Figure S2. Effect of chloroquine on high K+-induced contraction and intracellular Ca2+ increment in aortic smooth muscle after the restoration of Ca2+ 973 Research Program - No. 2011CB809104 istex:9A78879F7E127EA26C23CC5670488295173414C2 ark:/67375/WNG-T0SP4S58-X ArticleID:CEP12217 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0305-1870 1440-1681 |
DOI: | 10.1111/1440-1681.12217 |