Dual immunosuppression enhances vasomotor injury: Interactive effect between endothelin-1 and nitric oxide bioavailability

Ramzy, Danny; Tumiati, Laura C.; Tepperman, Elissa; Sheshgiri, Rohit; Jackman, Jessica; Badiwala, Mitesh; Rao, Vivek

doi:10.1016/j.jtcvs.2007.09.075

Cited by 11 publications

(12 citation statements)

References 34 publications

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“…[1][2][3][4] Our group has shown that CsA treatment yields vasomotor dysfunction characterized by impairment in vasorelaxation and increased sensitivity to vasospasm as a result of changes in NO/ET regulation. [5][6][7] Although tacrolimus (Tac) has yet to demonstrate a major difference in rescuing the allograft from refractory rejection or preventing AV, the vascular effects appear more promising. Overall, the literature supports Tac as having a more favorable vascular profile, particularly with regard to two important cardiovascular risk factors: hypertension and dyslipidemia.…”

mentioning

confidence: 99%

“…Although not a transplant model, this was chosen deliberately to evaluate the vascular effects directly related to immunosuppressant exposure, without the confounding factors associated with transplantation such as ischemia/reperfusion injury and host immune response. [5][6][7] Methods Animal care conformed strictly to the Canadian Council on Animal Care's Guide for the Care and Use of Experimental Animals. 8 Male Lewis rats (250 to 350 g, n ϭ 8 per group) were administered the drug of interest (saline control or Tac at 0.5, 1.5 or 3 mg/kg/ day) via intraperitoneal injection for a period of 14 days prior to assessment of vasomotor function.…”

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confidence: 99%

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Tacrolimus preserves vasomotor function and maintains vascular homeostasis

Tepperman

Tumiati

Ramzy

et al. 2011

The Journal of Heart and Lung Transplantation

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confidence: 99%

mentioning

confidence: 99%

Tacrolimus preserves vasomotor function and maintains vascular homeostasis

Tepperman

Tumiati

Ramzy

et al. 2011

The Journal of Heart and Lung Transplantation

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“…GC treatment in animals leads to impaired endothelial function [24, 25]. As regards the mechanisms involved (Fig.…”

Section: Direct Effects Of Gcs On Endothelial Cells and Functionmentioning

confidence: 99%

“…As regards the mechanisms involved (Fig. 1), decreased vascular availability in NO, the major mediator of endothelial function produced by the vascular endothelial NO synthase (eNOS), has been demonstrated [25], which is secondary to decreased eNOS activity [26], eNOS expression [25], eNOS gene transcription [24], increased degradation of eNOS mRNA [27], decreased eNOS protein stability [24], inhibition of calcium mobilization in endothelial cells [26] or reduction of tetrahydrobiopterin levels, a cofactor required for eNOS enzyme activity [28]. Besides decreasing eNOS activity/expression, GCs have beem found to reduce vascular NO bioavailability by increasing reactive oxygen species (ROS) production.…”

Section: Direct Effects Of Gcs On Endothelial Cells and Functionmentioning

confidence: 99%

“…Regarding EDHF, in a rat model of prenatal dexamethasone exposure, GC was responsible for an imbalance between EDHF and EDCF production, to the detriment of EDHF in the aorta [31]. GCs are also responsible for increased sensibility to endothelium-derived vasoconstrictors, such as endothelin-1 [25, 32]. …”

Section: Direct Effects Of Gcs On Endothelial Cells and Functionmentioning

confidence: 99%

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Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid arthritis

et al. 2016

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Rheumatoid arthritis (RA) is the most common systemic autoimmune disease characterized by articular and extra-articular manifestations involving cardiovascular (CV) diseases. RA increases the CV mortality by up to 50 % compared with the global population and CV disease is the leading cause of death in patients with RA. There is growing evidence that RA favors accelerated atherogenesis secondary to endothelial dysfunction (ED) that occurs early in the course of the disease. ED is a functional and reversible alteration of endothelial cells, leading to a shift of the actions of the endothelium towards reduced vasodilation, proinflammatory state, proliferative and prothrombotic properties. The mechanistic links between RA and ED have not been fully explained, but growing evidence suggests a role for traditional CV factors, auto-antibodies, genetic factors, oxidative stress, inflammation and iatrogenic interventions such as glucocorticoids (GCs) use. GCs have been used in RA for several decades. Whilst their deleterious CV side effects were described in the 1950s, their effect on CV risk associated with inflammatory arthritis remains subject for debate. GC might induce negative effects on endothelial function, via a direct effect on endothelium or via increasing CV risk factors. Conversely, they might actually improve endothelial function by decreasing systemic and/or vascular inflammation. The present review summarizes the available data on the impact of GCs on endothelial function, both in normal and inflammatory conditions, with a special focus on RA patients.

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Efficacy of synthetic glucocorticoids in COVID-19 endothelites

Ferrara

Vitiello

2021

Naunyn-Schmiedeberg's Arch Pharmacol

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Since March 2020, the world has been fighting a global pandemic caused by a new coronavirus SARS-CoV-2 (COVID-19). SARS-CoV-2 is responsible for severe acute respiratory syndrome, an airway disease that can be severe and fatal in a percentage of cases. Patients with severe COVID-19 can develop extrapulmonary lesions, with renal, hepatic, cardiac, neurological, and tissue involvement that can cause further severe complications. On December 21, 2021, the European Medicines Agency (EMA) authorized the marketing of the first COVID-19 vaccine. However, several randomized trials are ongoing to find effective, safe, and widely available treatments. The most severe stages of COVID-19 infection are characterized by a multi-system inflammatory state induced by a cytokine storm causing multi-organ injury. Epidemiologic evidence has shown that glucocorticoids (GCs), particularly dexamethasone, are used in severe, hospitalized patients with COVID-19 with good therapeutic benefit. COVID-19 can also damage the endothelial system, causing microcirculatory disturbances and consequently leading to functional organ disorders. The combination of endothelial dysfunction with a generalized inflammatory state may contribute to the general pro-coagulative state described in patients with COVID-19 with increased risk of venous and arterial occlusions. The aim of this article is to describe the therapeutic utility of GCs in stabilizing the vascular endothelial barrier in COVID-19 infection. Indeed, we believe that the stabilization of the endothelial barrier and the anti-inflammatory effect of GCs could be the main effect underlying the therapeutic efficacy in COVID-19 patients.

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Dual immunosuppression enhances vasomotor injury: Interactive effect between endothelin-1 and nitric oxide bioavailability

Abstract: Cyclosporine A and hydrocortisone induce vasomotor dysfunction with a synergistic impairment observed after concomitant exposure. Our findings suggest that the resultant vasomotor dysfunction is the result of alterations in both nitric oxide and endothelin-1 regulation.

Cited by 11 publications

References 34 publications

Tacrolimus preserves vasomotor function and maintains vascular homeostasis

Tacrolimus preserves vasomotor function and maintains vascular homeostasis

Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid arthritis

Efficacy of synthetic glucocorticoids in COVID-19 endothelites

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