Endothelium-independent vasorelaxant effect of sodium ferulate on rat thoracic aorta

Aims: This study was designed to investigate the effects of sodium ferulate (SF) on rat isolated thoracic aortas and the possible mechanisms. Main ethods: Isometric tension was recorded in response to drugs in organ bath. Cytorsolic free Ca2+ concentration ([Ca2+](i)) was measured using Fluo-3 in cultured rat aortic smooth muscle cells (RASMC). Key findings: 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 2 endothelium did not significantly modify the SF-induced relaxation. In Ca2+-free solution, SF noticeably inhibited extracellular Ca2+-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 Ca2+ . with the pD(2) of 2.9 +/- 0.03. In RASMC, SF had no effect on PE- or KCI-induced [Ca2+](i), increase either in the presence or in the absence of external Ca2+. Significance: These results indicate that SF acts directly as a non-selective relaxant to vascular smooth muscle. The direct inhibition of the common pathway after [Ca2+], increase may account for the SF-induced relaxation in Ca2+-dependent contraction, while the blockage of the PKC-mediated contractile mechanism is likely responsible for the SF-induced relaxation in Ca2+-independent contraction. (C) 2008 Elsevier Inc. All rights reserved.