Glucocorticoid excess and hypertension

Baid, Smita; Nieman, Lynnette K.

doi:10.1007/s11906-004-0046-0

Cited by 65 publications

(47 citation statements)

References 53 publications

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“…On the other hand, nitric oxide system has also been implicated in glucocorticoid induced hypertension [42,43]. Therefore, the involvement of pathways other than AT 1 receptor in glucocorticoid-mediated hypertension and oxidative stress may also be possible [42][43][44]. In overall, it is likely that excessive use of this anti-inflammatory drug could evoke Ang II pathway leading to cardiotoxicity in the long run.…”

Section: Discussionmentioning

confidence: 99%

Excess of Glucocorticoid Induces Cardiac Dysfunction via Activating Angiotensin II Pathway

Roy

Mukherjee

et al. 2009

Cell Physiol Biochem

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Background: Glucocorticoid is widely used as an anti-inflammatory drug in various diseases however excess of it often causes cardiovascular complications. The present study was undertaken to understand the molecular mechanism of glucocorticoid-induced cardiac dysfunction. Methods: Rats were treated daily with synthetic glucocorticoid, dexamethasone with or without mifepristone or losartan up to 15 days. Hemodynamic parameters were measured by PV-loop method using Millar’s instrument. Cardiac remodelling, fibrosis and oxidative stress were monitored after 15 days. Results: The systolic blood pressure was increased whereas the heart beat and cardiac output (n=6) were decreased by dexamethasone. Dexamethasone caused increase in the heart weight to body weight ratio (P<0.001, n=20), increased level of mRNA of atrial natriuretic peptide and an increased deposition of collagens in the extracellular matrix of the left ventricle which were inhibited by both mifepristone and losartan. The rate of oxygen consumption was decreased in association with increased levels of hypoxia inducible factor 1α, lipid peroxidation (P<0.01, n=3) and superoxide dismutase activity (P<0.01, n=3) in dexamethasone treated rat heart. All these changes were reversed by mifepristone and losartan. Conclusions: The excess of glucocorticoid induces cardiac remodelling and pathophysiolgical changes of the myocardium via angiotensin II signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Excess of Glucocorticoid Induces Cardiac Dysfunction via Activating Angiotensin II Pathway

Roy

Mukherjee

et al. 2009

Cell Physiol Biochem

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“…Indeed, mice exposed to corticosterone had higher mean arterial pressure compared with vehicle-treated mice. As GCs act by nonspecific binding on the MR in the kidney, sodium retention and potassium excretion increases (Baid & Nieman 2004). Concomitantly, water retention increases, resulting in augmented plasma volume and thus elevation of blood pressure.…”

Section: A Model Mimicking the Metabolic Syndromementioning

confidence: 99%

β-cell adaptation in a mouse model of glucocorticoid-induced metabolic syndrome

Fransson¹,

Franzén²,

Rosengren³

et al. 2013

Journal of Endocrinology

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Glucocorticoids (GCs) are stress hormones primarily responsible for mobilizing glucose to the circulation. Due to this effect, insulin resistance and glucose intolerance are concerns in patients with endogenous overproduction of GCs and in patients prescribed GC-based therapy. In addition, hypercortisolemic conditions share many characteristics with the metabolic syndrome. This study reports on a thorough characterization, in terms of glucose control and lipid handling, of a mouse model where corticosterone is given via the drinking water. C57BL/6J mice were treated with corticosterone (100 or 25 mg/ml) or vehicle in their drinking water for 5 weeks after which they were subjected to insulin or glucose tolerance tests. GC-treated mice displayed increased food intake, body weight gain, and central fat deposit accumulations. In addition, the GC treatment led to dyslipidemia as well as accumulation of ectopic fat in the liver and skeletal muscle, having a substantial negative effect on insulin sensitivity. Also glucose intolerance and hypertension, both part of the metabolic syndrome, were evident in the GC-treated mice. However, the observed effects of corticosterone were reversed after drug removal. Furthermore, this study reveals insights into b-cell adaptation to the GC-induced insulin resistance. Increased pancreatic islet volume due to cell proliferation, increased insulin secretion capacity, and increased islet chaperone expression were found in GC-treated animals. This model mimics the human metabolic syndrome. It could be a valuable model for studying the complex mechanisms behind the development of the metabolic syndrome and type 2 diabetes, as well as the multifaceted relations between GC excess and disease.

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“…Despite this, plasma renin activity and plasma renin concentration are generally normal or suppressed in patients with CS, suggesting that there is an overall increased throughput in the system [8]. Moreover, patients with CS show an increased pressor response to angiotensin II, suggesting increased sensitivity to the agent.…”

Section: Pathogenesis Of Hypertension In Csmentioning

confidence: 99%

Hypertension in Cushing’s Syndrome: From Pathogenesis to Treatment

Cicala

Mantero²

2010

Neuroendocrinology

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Hypertension is one of the most distinguishing features of endogenous Cushing’s syndrome (CS), as it is present in about 80% of adult patients whereas in children its prevalence is about 47%. Hypertension in CS is significantly correlated with the duration of hypercortisolism and results from the interplay between several pathophysiological mechanisms regulating plasma volume, peripheral vascular resistance and cardiac output, all of which are increased in this state. Glucocorticoids cause hypertension through several mechanisms: their intrinsic mineralocorticoid activity; through activation of the renin-angiotensin system; by enhancement of vasoactive substances, and by causing suppression of the vasodilatory systems. In addition, glucocorticoids may exert some hypertensive effects on cardiovascular regulation through the CNS via both glucocorticoid and mineralocorticoid receptors. Hypertension in CS usually resolves with surgical removal of the tumor, but some patients require pharmacological antihypertensive treatment both pre- and postoperatively. Thiazides and furosemide should be avoided, while adrenergic blockade and calcium channel antagonists are usually ineffective. Mineralocorticoid receptor antagonists, Ang II blockers and ACE inhibitors are good anti-hypertensive options; PPAR-γ agonists may help in many aspects of the insulin resistance syndrome. The relatively selective glucocorticoid receptor antagonist Mifepristone (RU 486) could reduce blood pressure in patients with CS. Neuromodulatory agents such as the serotonin inhibitors cyproheptadine and ritanserin, valproid acid, dopamine agonists, somatostatin analogs may occasionally be effective, as well as drugs acting directly at the adrenal levels, such as Ketoconazole and aminoglutetimide or even opDDD. Treating hypertension in CS remains a difficult task and a big challenge, in order to decrease the morbidity and mortality associated with the disease.

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Glucocorticoid excess and hypertension

Cited by 65 publications

References 53 publications

Excess of Glucocorticoid Induces Cardiac Dysfunction via Activating Angiotensin II Pathway

Excess of Glucocorticoid Induces Cardiac Dysfunction via Activating Angiotensin II Pathway

β-cell adaptation in a mouse model of glucocorticoid-induced metabolic syndrome

Hypertension in Cushing’s Syndrome: From Pathogenesis to Treatment

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