trans-sodium-crocetinate and Hypertension

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.. 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.. 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.. 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.

Topics: Animals; Aorta; Carotenoids; Crocus; Disease Models, Animal; Esters; Hypertension; Male; Muscle, Smooth, Vascular; Plant Extracts; Rats; Rats, Inbred SHR; Vitamin A

Crocetin is a natural carotenoid dicarboxylic acid that is found in the fruit of Gardenia jasminoides Ellis (Cape Jasmine) and in the stamen and pistil of Crocus sativus L. (saffron). It is used worldwide as an important spice, food colorant, and herbal medicine. In the current investigation, we have examined the cardiovascular effects of crocetin using stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs (6 weeks old) were classified into three groups: a control group and two crocetin groups (25 and 50 mg/kg/day). The animals were given crocetin for 3 weeks. Body weights in each group were not significantly different during the treatment period, but the increase in systolic blood pressures observed with age was significantly moderated by crocetin. Thrombogenesis, assessed using a He-Ne laser technique in pial vessels, was significantly decreased. Antioxidant activity, assessed by measuring urinary 8-hydroxy-2'-deoxyguanosine levels, together with urinary nitric oxide (NO) metabolite levels, was increased significantly after treatment. Acetylcholine-induced vasodilation was measured using the aorta and indicated that endothelial function was significantly improved by crocetin. These results strongly suggest that the antihypertensive and antithrombotic effects of crocetin were related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Carotenoids; Crocus; Fruit; Gardenia; Hypertension; Intracranial Thrombosis; Male; Nitric Oxide; Oxidative Stress; Rats, Inbred SHR; Vasodilation; Vitamin A

Hypertension is associated with endothelial dysfunction characterized by decreased vasorelaxation. Crocetin, a bioactive compound of saffron, exhibits favorable cardiovascular properties. We analyze the vasomodulatory effects of crocetin in hypertension.. Myographical experiments were performed to compare the relaxation induced by acetylcholine (ACH) on aortic rings from normotensive (Wistar) and hypertensive (SHR) rats, incubated with or without crocetin or saffron extract and L-NAME or indomethacin. Extracts were also assayed in deendothelialized rings. UV-vis spectrophotometry and HPLC-DAD were used to characterize and quantify the saffron used.. Crocetin enhanced the ACH relaxations in aorta from hypertensive (strongly) and normotensive rats (weakly). Saffron extract did not modify this. Crocetin plus L-NAME abolished the relaxant response in SHR but not in Wistar aorta. Crocetin plus indomethacin did not modify the indomethacin response in either SHR or Wistar aorta. Crocetin in rubbed segments did not modify the ACH responses. In contrast, saffron increased this response in rubbed segments from SHR but not Wistar rats.. Crocetin exerts healthy vasomodulatory effects in hypertension, strongly improving endothelium-dependent ACH relaxations via endothelial nitric oxide but not the cyclooxygenase pathway. This work proposes that crocetin supplements are a possible complement in the therapy of hypertension.

Topics: Acetylcholine; Animals; Antihypertensive Agents; Carotenoids; Crocus; Cyclooxygenase Inhibitors; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertension; Male; Myography; Nitric Oxide; Nitric Oxide Synthase; Phytotherapy; Plants, Medicinal; Rats, Inbred SHR; Rats, Wistar; Vasodilation; Vasodilator Agents; Vitamin A