Aqueous-methanolic extract of sweet flag (Acorus calamus) possesses cardiac depressant and endothelial-derived hyperpolarizing factor-mediated coronary vasodilator effects

This investigation was aimed to probe the pharmacological base of medicinal use of Acorus calamus in ischemic heart diseases. Effect on heart parameters wasstudied in isolated rabbit heart while coronary vasodilatoreffect was studied in isolated bovine coronary arterialrings, suspended in tissue baths filled with Krebs solution,maintained at 37°C, aerated with carbogen and responseswere measured on PowerLab data acquisition system. InLangendorrf's perfused rabbit heart, the crude extract ofAcorus calamus (Ac.Cr) at 0.01-10 mg/mL partially suppressedforce of ventricular contractions (FVC), heart rate(HR) and coronary flow (CF). The ethylacetate fractioncompletely suppressed FVC, partially suppressed HR andCF, while the nHexane fraction exhibited similar effect onFVC and HR but increased CF, similar to methacholine andarachidonic acid. In bovine coronary arterial preparations,Ac.Cr caused inhibition of U46619 (20 nM)-precontractions,which was blocked in presence of increasing concentrationof K ⁺ (4.8-20 mM), tetraethylammonium(1 μM) and SKF525A (10 μM), similar to arachidonic acidand methacholine, indicating K ⁺ channels activation andpossible involvement of endothelial-derived hyperpolarizingfactor (EDHF). Activity-directed fractionation revealedthat EDHF-mediated activity is concentrated in the nHexanefraction. When tested against high K ⁺, the ethylacetatefraction was found more potent than parent crude extract and nHexane fraction. These data indicate that Ac.Crmediates coronary vasodilator effect primarily throughEDHF, responsible for the increase in CF, while the cardiacdepressant effects may be due to the presence of additionalcardiac depressant constituent(s), thus provides possiblemechanistic basis to its medicinal use in ischemic heartdiseases.