Abstract

Background: Endothelial dysfunction, characterized by an enhancement in vasoconstriction, is clearly associated with hypertension. Saffron (Crocus sativus L.) bioactive compounds have been recognized to have hypotensive properties. Recently, we have reported that crocetin exhibits potent vasodilator effects on isolated aortic rings from hypertensive rats. In this work, we have aimed to analyze the anticontractile ability of crocetin or crocetin esters pool (crocins) isolated from saffron. Thus, we have studied the effects of saffron carotenoids on endothelium-dependent and -independent regulation of smooth muscle contractility in genetic hypertension. Methods: We have measured the isometric responses of aortic segments with or without endothelium obtained from spontaneously hypertensive rats. The effects of carotenoids were studied by assessing the endothelial modulation of phenylephrine-induced contractions (10−9–10−5 M) in the presence or absence of crocetin or crocins. The role of nitric oxide and prostanoids was analyzed by performing the experiments with L-NAME (NG-nitro-l-arginine methyl ester) or indomethacin (both 10−5 M), respectively. Results: Crocetin, and to a minor extent crocins, diminished the maximum contractility of phenylephrine in intact rings, while crocins, but not crocetin, increased this contractility in de-endothelizated vessels. In the intact vessels, the effect of crocetin on contractility was unaffected by indomethacin but was abolished by L-NAME. However, crocetin but not crocins, lowered the already increased contractility caused by L-NAME. Conclusions: Saffron compounds, but especially crocetin have endothelium-dependent prorelaxing actions. Crocins have procontractile actions that take place via smooth muscle cell mechanisms. These results suggest that crocetin and crocins activate different mechanisms involved in the vasoconstriction pathway in hypertension.

Highlights

  • Crocetin esters and crocetin (CCT), carotenoids present in the dried stigmas of Crocus sativus L.(saffron), are considered the pharmacologically active components of saffron [1]

  • It is important to characterize the saffron used in studies in order to determine its quality. This is correlated with its amount in crocetin esters, picrocrocin, and safranal, because these compounds are responsible for its bioactive properties

  • The chromatographic purity of the compounds identified as crocetin esters, safranal, and picrocrocin correspond to the 99.9% absorbance at 440 nm, 95.3% at 330 nm, and 96.1% at 250 nm, respectively

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Summary

Introduction

Crocetin esters and crocetin (CCT), carotenoids present in the dried stigmas of Crocus sativus L.(saffron), are considered the pharmacologically active components of saffron [1]. Regarding the cardiovascular effects of saffron, previous studies revealed that this spice or its constituents possess hypotensive effects [12,13,14,15,16]. These studies showed that extracts of saffron petals reduced mean arterial blood pressure in rats. Hypotensive effects have been reported for aqueous and ethanol extracts of saffron stigmas and for two active constituents of this plant, crocin and safranal [15,16]. The role of nitric oxide and prostanoids was analyzed by performing the experiments with L-NAME (NG-nitro-L-arginine methyl ester) or indomethacin (both 10−5 M), respectively

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