Effects of Crocetin Esters and Crocetin from Crocus sativus L. on Aortic Contractility in Rat Genetic Hypertension.

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.