Endothelium-independent vasorelaxant effect of sodium ferulate on rat thoracic aorta.
OBJECTIVE
This study was designed to investigate the effects of sodium ferulate (SF) on rat isolated thoracic aortas and the possible mechanisms.


METHODS
Isometric tension was recorded in response to drugs in organ bath. Cytosolic free Ca(2+) concentration ([Ca(2+)](i)) was measured using Fluo-3 in cultured rat aortic smooth muscle cells (RASMC).


RESULTS
SF (0.1-30 mM) relaxed the isolated aortic rings precontracted with phenylephrine (PE) and high-K(+) in a concentration-dependent manner with respective pD(2) of 2.7+/-0.02 and 2.6+/-0.06. Mechanical removal of endothelium did not significantly modify the SF-induced relaxation. In Ca(2+)-free solution, SF noticeably inhibited extracellular Ca(2+)-induced contraction in high-K(+) and PE pre-challenged rings, and suppressed the transient contraction induced by PE and caffeine. The vasorelaxant effect of SF was unaffected by various K(+) channel blockers such as tetraethylammonium, glibenclamide, 4-aminopyridine, and barium chloride. In addition, SF concentration-dependently reduced the contraction induced by phorbol-12-myristate-13-acetate, an activator of protein kinase C (PKC), in the absence of extracellular Ca(2+), with the pD(2) of 2.9+/-0.03. In RASMC, SF had no effect on PE- or KCl-induced [Ca(2+)](i) increase either in the presence or in the absence of external Ca(2+).


CONCLUSIONS
These results indicate that SF acts directly as a non-selective relaxant to vascular smooth muscle. The direct inhibition of the common pathway after [Ca(2+)](i) increase may account for the SF-induced relaxation in Ca(2+)-dependent contraction, while the blockage of the PKC-mediated contractile mechanism is likely responsible for the SF-induced relaxation in Ca(2+)-independent contraction.
Chen
Guo-Ping
GP
Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China.
Ye
Yang
Y
Li
Liang
L
Yang
Yin
Y
Qian
An-Bin
AB
Hu
Shen-Jiang
SJ
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003373:Coumaric Acids / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*
D003373:Coumaric Acids; D010656:Phenylephrine; D011189:Potassium Chloride; C004999:ferulic acid; D002118:Calcium