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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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a cluster of metabolic and cardiovascular symptoms: insulin resistance (IR), obesity, dyslipemia. Hypertension and vascular disorders are central to this syndrome. After a brief historical review, we discuss the role of sympathetic tone. Subsequently, we examine the link between endothelial dysfunction and IR. NO is involved in the insulin-elicited capillary vasodilatation. The insulin-signaling pathways causing NO release are different to the classical. There is a vasodilatory pathway with activation of NO synthase through Akt, and a vasoconstrictor pathway that involves the release of endothelin-1 via MAPK. IR is associated with an imbalance between both pathways in favour of the vasoconstrictor one. We also consider the link between hypertension and IR: the insulin hypothesis of hypertension. Next we discuss the importance of perivascular adipose tissue and the role of adipokines that possess vasoactive properties. Finally, animal models used in the study of vascular function of metabolic syndrome are reviewed. In particular, the Zucker fatty rat and the spontaneously hypertensive obese rat (SHROB).This one suffers macro- and microvascular malfunction due to a failure in the NO system and an abnormally high release of vasoconstrictor prostaglandins, all this alleviated with glitazones used for metabolic syndrome therapy. [ABSTRACT FROM AUTHOR]

Glitazones exhibit beneficial effects in the vascular system, both on large vessels and at a microcirculatory level. We previously reported the effects of glitazones in the aorta of spontaneously hypertensive rats (SHR). We focus now on the acute and long-term actions of these drugs on mesenteric resistance arteries of the SHR. Incubation with pioglitazone or rosiglitazone (10-5 mol/l) improved endothelium-dependent relaxations to acetylcholine and the endothelial modulation of phenylephrine contractions. Acetylcholine relaxations that were abolished by NG-nitro-L-arginine methylester were partly recovered by the glitazones, but no effects of these drugs were observed in the presence of indomethacin or indomethacin + L-NAME. Glitazones did not change the contractions to U46619 or the endothelium-independent relaxation to sodium nitroprusside. Three-week oral pioglitazone or rosiglitazone treatment (3 and 10 mg/kg/day, respectively) confirmed the acute experiments. Thus, in microvessels, glitazones improve endothelial function in such a way that they do not alter endothelial nitric oxide release but reduce the production of vasoconstrictor prostanoids from endothelial cells. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Glitazones have beneficial antihypertensive effects independent of their insulin-sensitizing action. We have studied the effects of pioglitazone and rosiglitazone on the endothelial ability to counteract vascular smooth muscle contractility in genetic hypertension. To achieve this, we measured isometric responses of aortic segments obtained from spontaneously hypertensive rats. The effects of glitazones on endothelial function were studied by assessing the endothelial modulation of phenylephrine-induced isometric contractions (10−9–10−5 M) in the presence or absence of pioglitazone or rosiglitazone (10−5 M), added directly to an organ bath or orally administered to the rats (pioglitazone, 10 mg/kg). The role of both NO and prostanoids was analyzed by performing experiments in the presence of N G-nitro-l-arginine methyl ester (l-NAME) and/or indomethacin (both 10−5 M) in the organ bath. Concentration-dependent contractions to l-NAME (10−6–3×10−4 M) in the presence or absence of glitazones were carried out as an estimation of basal NO release. Pioglitazone, but not rosiglitazone, increased contractile responses to phenylephrine in intact vessels. The contractile responses to phenylephrine obtained in the presence of glitazones were markedly diminished by indomethacin, but enhanced by l-NAME. Analogous results were obtained in aortas from pioglitazone-chronically treated animals. l-NAME concentration-dependent contractions were enhanced by both glitazones. Both glitazones lowered the sensitivity to acetylcholine (10−9–10−5 M). In conclusion, pioglitazone and rosiglitazone alter vascular function differentially and through endothelium-dependent mechanisms. These drugs act over the same pathways on the endothelium where they have a dual action, increasing both production of vasoconstrictor prostanoids and NO. The balance between both vasoactive substances determines the vascular response to glitazones. [Copyright &y& Elsevier]