Bitter tastants induce relaxation of rat thoracic aorta precontracted with high K+

Wen Bo Sai, Meng Fei Yu, Ming Yu Wei, Zhongju Lu, Yun Min Zheng, Yong Xiao Wang, Gangjian Qin, Donglin Guo, Guangju Ji, Jinhua Shen, Qing Hua Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)301-308
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume41
Issue number4
DOIs
StatePublished - Apr 1 2014

Keywords

  • Bitter tastants
  • Chloroquine
  • Intracellular Ca
  • L-type Ca channels
  • Patch clamp
  • Relaxation

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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