The Effects And Mechanisms Of Phenolic Acids On Isolated Thoracic Aortic Rings From Rats

Objective：This study was designed to investigate the effects of phenolicacids active compounds including Ferulic acid （FA）, Caffeic acid （CA）,p-Coumaric acid （p-CA） on rat isolated thoracic aortas and the possiblemechanisms, futher explor the relation between chemical structures andbiological efficacy.Methods: Using isolated vascular methods, the vasodilatory effects ofFA （0.5to4mmol/L）, CA （1to10mmol/L）, p-CA （1to8mmol/L） wereevaluated basing on the pre-contracted thoracic aortic rings induced byL-phenylephrine hydrochloride （PE） and KCl. After incubating with the drugsof NG-nitro-L-arginine methylester （L-NAME）, Glibenclamide （Gli）,Indomethacin （Indo）, Tetraethylammonium （TEA）, Methylene blue （MB）,Verapamil, the vasodilatation effects of phenolic acids active compound werealso observed. And in Ca²⁺-free Krebs-henseleit solution, the influence of FA,CA, p-CA on thoracic aortic rings preconstricted with PE was observed.Statistical comparisons were made with the version13.0of SPSS soft ware.Results:1Phenolic acids of FA （0.5to4mmol/L）, CA （1to10mmol/L）, p-CA （1to8mmol/L） relaxed the isolated aortic rings precontracted withL-phenylephrine hydrochloride （PE） and KCl in a concentration-dependentmanner. The EC50（mmol/L） of three phenolic acids relaxing thoracic aorticrings preconstricted with PE was2.43±0.52,5.51±0.40, and4.37±0.40,respectively. With KCl, this EC50（mmol/L） was2.17±0.15,5.53±0.38, and4.37±0.57, respectively. The vasorelaxation efficacy of FA, CA, p-CA wassignificantly different （P<0.05）, the order of the vasodilator effect was FA>p-CA> CA.2The values of pD2of FA on PE precontracted aortas rings with or without endothelium were2.62±0.08and2.60±0.93, respectively （P>0.05）.The values of pD2of CA were2.26±0.03and2.26±0.03, respectively （P>0.05）. The values of pD2of p-CA were2.36±0.04and2.36±0.03, respectively（P>0.05）. Mechanical removal of endothelium did not significantly modifythe phenoic acids-induced vasorelaxation.3NG-nitro-L-arginine methylester （Nitric oxide synthesis inhibitor）,Glibenclamide （ATP-sensitive K+channels blocker）, Indomethacin（cyclooxygenase inhibitor）, Tetraethylammonium (Ca²⁺-activated K+channelsblocker), Methylene blue （Guanylate cyclase inhibitor） did not inhibit FA, CA,p-CA-induced vasorelaxation （P>0.05）.4In Ca²⁺-free K-H solution, FA, CA, p-CA significantly inhibitedextracellular Ca²⁺-induced contraction in a concentration-dependent manner inPE pre-challenged rings, and also suppressed the intracellular Ca²⁺-inducedtransient contraction induced by PE. The biological activities of inhibitingCa²⁺-induced contraction of the three phenolic acids were different, FA hadstronger effect, CA and p-CA had similar biological activity.Conclusion:1FA, CA, p-CA relaxed the isolated thoracic aortic rings of rats evokedby PE and KCl in an concentration-dependent manner, and the vasorelaxationeffect was independent-endothelium.2The vasorelaxing effect of FA, CA, p-CA did not be associated with theendothelium pathway and K+channels pathway, but FA, CA, p-CAantagonized the contractile effects of Ca²⁺. These results suggested that thevasorelaxing effect of FA, CA, p-CA was mediated mainly through inhibitingCa²⁺release from intracellular stores and extracellular Ca²⁺influx intovascular smooth muscle cells.3The differences in the chemical structures of these phenolic acid activecompound FA, CA, p-CA alter both their biological efficacy andbioavailability. The differences of chemical structure group （hydroxyl andmethyl） position and number lead to the difference of vasorelaxation ability,FA> p-CA> CA.