Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

Davel, Ana Paula; Wenceslau, Camilla F; Akamine, Eliana Hiromi; Xavier, Fabiano E.; Couto, Gisele Kruger; Oliveira, H.T.; Rossoni, Luciana Venturini

doi:10.1590/s0100-879x2011007500104

Cited by 74 publications

(65 citation statements)

References 57 publications

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“…A defect in the function of endothelial cells, which can occur in response to abnormal conditions such as ageing and metabolic disease, is a hallmark of vascular pathology and a predictor of major cardiovascular events Davel et al, 2011). The function of endothelial cells is controlled by numerous physiological and exogenous molecules in the circulation, including medicines and dietary derivatives such as eugenol.…”

Section: Discussionmentioning

confidence: 99%

Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels

Peixoto‐Neves

Wang

Leal-Cardoso

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEEugenol, a vanilloid molecule found in some dietary plants, relaxes vasculature in part via an endothelium-dependent process; however, the mechanisms involved are unclear. Here, we investigated the endothelial cell-mediated mechanism by which eugenol modulates rat mesenteric artery contractility and systemic BP. EXPERIMENTAL APPROACHThe isometric tension of rat mesenteric arteries (size 200-300 μm) was measured using wire myography; non-selective cation currents (ICat) were recorded in endothelial cells using patch clamp electrophysiology. Mean arterial pressure (MAP) and heart rate (HR) were determined in anaesthetized rats. KEY RESULTSEugenol relaxed endothelium-intact arteries in a concentration-dependent manner and this effect was attenuated by endothelium denudation. L-NAME, a NOS inhibitor, a combination of TRAM-34 and apamin, selective blockers of intermediate and small conductance Ca 2+ -activated K + channels, respectively, and HC-067047, a TRPV4 channel inhibitor, but not indomethacin, a COX inhibitor, reduced eugenol-induced relaxation in endothelium-intact arteries. Eugenol activated HC-067047-sensitive ICat in mesenteric artery endothelial cells. Short interfering RNA (siRNA)-mediated TRPV4 knockdown abolished eugenol-induced ICat activation. An i.v. injection of eugenol caused an immediate, transient reduction in both MAP and HR, which was followed by prolonged, sustained hypotension in anaesthetized rats. This sustained hypotension was blocked by HC-067047. CONCLUSIONS AND IMPLICATIONSEugenol activates TRPV4 channels in mesenteric artery endothelial cells, leading to vasorelaxation, and reduces systemic BP in vivo. Eugenol may be therapeutically useful as an antihypertensive agent and is a viable molecular candidate from which to develop second-generation TRPV4 channel activators that reduce BP. AbbreviationsEDHF, endothelium-derived hyperpolarizing factor; ICat, non-selective cation currents; IKCa, intermediate conductance calcium-activated potassium channel; MAP, mean arterial pressure; PGI2, prostacyclin; siRNA, short interfering RNA; SKCa, small conductance calcium-activated potassium channel; TRP, transient receptor potential BJP British Journal of Pharmacology

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Section: Discussionmentioning

confidence: 99%

Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels

Peixoto‐Neves

Wang

Leal-Cardoso

et al. 2015

British J Pharmacology

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“…The vascular endothelium has an important protective role against cardiovascular disease, by release endothelium factor, which modulates vascular tonus, inflammation, and coagulation and the release of nitric oxide (NO) has a central role in this protection [1,2]. NO induces vasodilation by different mechanisms in order to decrease the cytoplasmic calcium concentration [Ca 2+ ] in vascular smooth muscle cells [3].…”

Section: Introductionmentioning

confidence: 99%

In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation

Martinelli¹,

Rodrigues²,

Moraes³

et al. 2018

J Pharm Pharm Sci

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-Purpose. In endothelial cells, investigate if the soluble guanylate cyclase (sGC) activation or stimulation is able to potentiate the relaxation in vessels. Methods. Aortic and coronary rings with and without endothelium were placed in a myograph and cumulative concentration-effect curves for DETA-NO or ataciguat were performed. Nitric oxide (NO) were measured by fluorescence or by selective electrode in human umbilical endothelial cells (HUVECs) in response to some treatments, including ataciguat, 8-BrcGMP and A23187. Results. The presence of the endothelium potentiated the relaxation induced by DETA-NO in aortic and coronary rings. In addition, in aortic rings the endothelium potentiated the relaxation induced by ataciguat. In the presence of nitric oxide synthase (NOS) inhibitor, the endothelium effect was abolished to DETA-NO or ataciguat, in both vessels. Ataciguat, 8-Br-cGMP and A23187 were able to induce NO production in HUVECs cells. In the presence of NOS inhibitor, the NO production induced by ataciguat and 8-Br-cGMP was abolished. Conclusions. Our results suggest that in aortic and coronary rings the endothelium potentiates the relaxation induced by activation or stimulation of sGC through a mechanism dependent of NOS activation.

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“…59,60 Hyperglycemia exposure increases endothelin-1 secretion 61 and impairs NO bioavailability, both through reduced eNOS activity and increased NO destruction. Further, hyperglycemia in insulin resistance also increases vascular oxidative stress through uncoupling eNOS, [62][63][64] activating NADPH oxidase, 65 inhibiting ROS scavenging systems, 66 and stimulating mitochondrial ROS production. [67][68][69] Hypercholesterolemia also impairs endothelial function.…”

Section: Endothelial Dysfunction and Cardiovascular Riskmentioning

confidence: 99%

Cytoskeleton, cytoskeletal interactions, and vascular endothelial function

Wang¹,

Widlansky²

2012

CHC

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Abstract:Far from being inert, the vascular endothelium is a critical regulator of vascular function. While the endothelium participates in autocrine, paracrine, and endocrine signaling, it also transduces mechanical signals from the cell surface involving key cell structural elements. In this review, we discuss the structure of the vascular endothelium and its relationship to traditional cardiovascular risk factors and clinical cardiovascular events. Further, we review the emerging evidence that cell structural elements, including the glycocalyx, intercellular junctions, and cytoskeleton elements, help the endothelium to communicate with its environment to regulate vascular function, including vessel permeability and signal transduction via nitric oxide bioavailability. Further work is necessary to better delineate the regulatory relationships between known key regulators of vascular function and endothelial cell structural elements.

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Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

Cited by 74 publications

References 57 publications

Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels

Eugenol dilates mesenteric arteries and reduces systemic BP by activating endothelial cell TRPV4 channels

In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation

Cytoskeleton, cytoskeletal interactions, and vascular endothelial function

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