Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

Swaminathan, Krishnan; Davies, Justine; George, Jacob; Rajendra, N. S.; Morris, Andrew D.; Struthers, Allan D.

doi:10.1007/s00125-008-0972-5

Cited by 62 publications

(53 citation statements)

References 47 publications

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“…Spironolactone was reported to worsen glycemic control when it was used in poorly controlled hypertension and diabetes. 18 However, there was no difference in blood pressure, electrolytes, hyperglycemia, glucose intolerance and hyperinsulinemia between animals with and without spironolactone treatment in this study. Rigsby et al reported that treatment with spironolactone decreased ischemic cerebral infarct size in male spontaneously hypertensive stroke-prone rats (SHRSP); in contrast, spironolactone had no effect on infarct size in OVX-SHRSP.…”

Section: Discussioncontrasting

confidence: 54%

Improvement of cognitive impairment in female type 2 diabetes mellitus mice by spironolactone

Sakamoto

Mogi

Iwanami

et al. 2011

J Renin Angiotensin Aldosterone Syst

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Patients with type 2 diabetes mellitus (T2DM) exhibit more severe cognitive decline in females compared with males; however, the preventive approach to this gender-specific cognitive decline is still an enigma. Spironolactone is a potassiumsparing diuretic that also acts as an androgen receptor antagonist. Here, we investigated whether spironolactone attenuates cognitive impairment observed in female T2DM mice. Adult wild-type (WT) mice and an obese T2DM model, KKAy mice, were employed in this study. Cognitive function was evaluated by the shuttle avoidance test and Morris water maze test. Administration of spironolactone (50 mg/kg per day in chow) had no significant effect on blood pressure, glucose tolerance or insulin resistance. In WT mice, no significant sex difference in cognitive function was observed; however, treatment with spironolactone improved spatial memory in the water maze, especially in female WT mice. Administration of spironolactone markedly improved the cognitive decline in female KKAy mice up to the level in male KKAy mice. Spironolactone treatment also improved cognitive function in ovariectomized-KKAy mice, but failed to improve it in those with administration of estradiol (200 μg/kg per day). In diabetic mice, spironolactone improved impaired cognitive function observed in female mice, suggesting that spironolactone may prevent cognitive impairment associated with diabetes in females clinically.

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Section: Discussioncontrasting

confidence: 54%

Improvement of cognitive impairment in female type 2 diabetes mellitus mice by spironolactone

Sakamoto

Mogi

Iwanami

et al. 2011

J Renin Angiotensin Aldosterone Syst

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“…39 Average blood pressure at baseline was 162·7/88·9 mmHg, and was significantly reduced by spironolactone compared to placebo (mean reductions in systolic and diastolic blood pressures were 14·2 and 5·3 mmHg respectively). However, endothelium-dependent vasodilatation in response to acetylcholine was not significantly improved by spironolactone.…”

Section: Raas Inhibition In the Clinical Settingmentioning

confidence: 89%

Role of aldosterone and angiotensin II in insulin resistance: an update

Lastra-Lastra

Sowers

Restrepo-Erazo

et al. 2009

Clinical Endocrinology

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SummaryThe role of the Renin-Angiotensin-Aldosterone system (RAAS) on the development of insulin resistance and cardiovascular disease is an area of growing interest. Most of the deleterious actions of the RAAS on insulin sensitivity appear to be mediated through activation of the Angiotensin II (Ang II) Receptor type 1 (AT 1 R) and increased production of mineralocorticoids. The underlying mechanisms leading to impaired insulin sensitivity remain to be fully elucidated, but involve increased production of reactive oxygen species and oxidative stress. Both experimental and clinical studies also implicate aldosterone in the development of insulin resistance, hypertension, endothelial dysfunction, cardiovascular tissue fibrosis, remodelling, inflammation and oxidative stress. There is abundant evidence linking aldosterone, through non-genomic actions, to defective intracellular insulin signalling, impaired glucose homeostasis and systemic insulin resistance not only in skeletal muscle and liver but also in cardiovascular tissue. Blockade of the different components of the RAAS, in particular Ang II and AT 1 R, results in attenuation of insulin resistance, glucose homeostasis, as well as decreased cardiovascular disease morbidity and mortality. These beneficial effects go beyond to those expected with isolated control of hypertension. This review focuses on the role of Ang II and aldosterone in the pathogenesis of insulin resistance, as well as in clinical relevance of RAAS blockade in the prevention and treatment of the metabolic syndrome and cardiovascular disease.

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“…Thus, eplerenone is a less potent yet better-tolerated alternative to spironolactone. Due to its anti-androgen effect, spironolactone treatment may slightly worsen glycemic control in patients with T2DM 74 , while eplerenone may have a mildly positive effect on glycemic control 75,76 .Meanwhile, finerenone is a heterobicyclic analog of naphthyridine derivatives. Finerenone is at least as potent as spironolactone but has a much better selectivity toward the MCR than eplerenone (about 500-fold greater).…”

Section: When Needed Select the Best Mcr Antagonist For Your Patientmentioning

confidence: 99%

Aldosterone and the mineralocorticoid receptor in insulin resistance and diabetes

Toloza

Mendivil

2020

ALAD

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Aldosterone is a key regulator of water and electrolyte metabolism, but recent evidence from multiple lines of research also identifies it as a major player in other chronic disorders, particularly diabetes and the metabolic syndrome. In this review, we summarize relevant aspects of aldosterone production, secretion, action, the way aldosterone and the mineralocorticoid receptor may impact energy metabolism, and useful take-home messages concerning mineralocorticoid antagonism in patients with type 2 diabetes mellitus. (Rev ALAD. 2017;7:203-11) RESUMENLa aldosterona es un regulador clave del metabolismo del agua y los electrólitos, pero la evidencia reciente de múltiples líneas de investigación también la identifica como un actor principal en otros trastornos crónicos, en particular en la diabetes y el síndrome metabólico. En esta revisión se resumen los aspectos relevantes de la producción de aldosterona, así como su secreción, su acción y la forma en que la aldosterona y el receptor mineralocorticoide pueden afectar al metabolismo energético, además de aportar información útil sobre el antagonismo mineralocorticoide en pacientes con diabetes mellitus de tipo 2.Palabras clave: Aldosterona. Metabolismo de los electrólitos. Diabetes. Síndrome Metabólico.

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Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

Cited by 62 publications

References 47 publications

Improvement of cognitive impairment in female type 2 diabetes mellitus mice by spironolactone

Improvement of cognitive impairment in female type 2 diabetes mellitus mice by spironolactone

Role of aldosterone and angiotensin II in insulin resistance: an update

Aldosterone and the mineralocorticoid receptor in insulin resistance and diabetes

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