Intracranial Aneurysm and Hemorrhagic Stroke in Glucocorticoid-remediable Aldosteronism

Litchfield, W. Reid; Anderson, Bruce F.; Weiss, Rachel B.; Lifton, Richard P.; Dluhy, Robert G.

doi:10.1161/01.hyp.31.1.445

Cited by 176 publications

(95 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Under these conditions, genetic abnormalities that markedly impact blood pressure variation should also materialize as stroke genes. For monogenic forms of hypertension, several reports of increased stroke frequency exist, including hypertension with brachydacytly (Bilginturan et al 1973), glucocorticoid remediable hypertension (Rich et al 1992;Litchfield et al 1998), apparent mineralocorticoid excess (New et al 1977), and Gordon's syndrome (PHA2).…”

Section: Hypertension and Strokementioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

View full text Add to dashboard Cite

Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

show abstract

Section: Hypertension and Strokementioning

confidence: 99%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

View full text Add to dashboard Cite

show abstract

“…A further concern is the high incidence of intracerebral haemorrhage (11-18%) with a high associated mortality (61%) at an early age (31.7 ± 11.3 years) among GRA-positive individuals. 15 In previous reports the youngest subject to suffer from an intracranial haemorrhage was 30 years of age, in this study the youngest individual to die from an intracranial haemorrhage was 17 years old. Although there is little detail about the effectiveness of antihypertensive treatment in preventing such catastrophic outcomes it must be assumed that the aggressive treatment of even borderline hypertension with amiloride, spironolactone or low-dose dexamethasone alone or in combination with other antihypertensive therapy should be expected to result in benefit.…”

Section: Discussionmentioning

confidence: 70%

Is random screening of value in detecting glucocorticoid-remediable aldosteronism within a hypertensive population?

et al. 2001

View full text Add to dashboard Cite

Introduction: Glucocorticoid-remediable aldosteronism (GRA) is a rare inherited cause for hypertension associated with a significant morbidity and mortality at an early age. Individuals with this abnormality frequently present with severe hypertension which is resistant to standard antihypertensive therapy, a strong family history of hypertension, intracranial haemorrhage, and sporadic hypokalaemia. However many affected individuals may appear phenotypically indistinguishable from normal essential hypertensives but remain at high risk of morbidity and mortality. Objective: To determine how effective random or targeted screening of hypertensive patients is for the detection of GRA. Design: A prospective study involving the screening of 300 hypertensive patients chosen at random attending the Aberdeen Hypertension Clinic and, during the same

show abstract

“…There are also several studies in humans showing a link between elevated plasma aldosterone and the risk of stroke. 16,17 Interestingly, a comparison of patients with essential hypertension and primary hyperaldosteronism suggests that the increased stroke risk in patients with primary hyperaldosteronism is blood pressure independent. 18 The blood pressure dependency of the response observed here remains unclear, and additional studies need to be carried out to evaluate this.…”

Section: Discussionmentioning

confidence: 99%

Mineralocorticoid Receptor Activation Causes Cerebral Vessel Remodeling and Exacerbates the Damage Caused by Cerebral Ischemia

2006

View full text Add to dashboard Cite

Abstract-Mineralocorticoid receptor antagonists protect against ischemic cerebrovascular disease; this appears to be caused by changes in cerebral vessel structure that would promote blood flow. Therefore, we hypothesized that mineralocorticoid receptor activation with deoxycorticosterone acetate would cause deleterious remodeling of the cerebral vasculature and exacerbate the damage caused by cerebral ischemia. Six-week-old male Wistar rats were treated with deoxycorticosterone acetate (200 mg/kg) for 6 weeks. At 12 weeks of age, the deoxycorticosterone acetate-treated rats had elevated systolic blood pressure compared with age-matched controls (157Ϯ5.9 versus 124Ϯ3.1 mm Hg deoxycorticosterone acetate versus control; PϽ0.05). The area of ischemic damage resulting from middle cerebral artery occlusion was greater in the deoxycorticosterone acetate-treated rats than control (63.5Ϯ3.72 versus 46.6Ϯ5.52% of the hemisphere infarcted, deoxycorticosterone acetate versus control; PϽ0.05). Middle cerebral artery structure was assessed using a pressurized arteriograph under calcium-free conditions. Over a range of intralumenal pressures, the lumen and ODs of the middle cerebral arteries were smaller in the deoxycorticosterone acetate-treated rats than the control rats (PϽ0.05). There was also an increase in the wall thickness and wall:lumen ratio in the vessels from deoxycorticosterone acetate-treated rats (PϽ0.05). The vessels from the deoxycorticosterone acetate-treated rats were stiffer than those from control rats as evidenced by a leftward shift in the stress/strain curve. These novel data suggest that mineralocorticoid receptor activation without salt loading and nephrectomy is sufficient to elicit deleterious effects on the cerebral vasculature that lead to inward hypertrophic remodeling and an increase in the ischemic damage in the event of a stroke. Key Words: mineralocorticoids Ⅲ cerebral ischemia Ⅲ remodeling Ⅲ cerebral arteries Ⅲ aldosterone S troke, in particular, ischemic stroke, is a leading cause of death and disability in the Western world. Yet, the factors that increase an individual's risk of having a stroke or exacerbate the damage caused by a stroke are still not completely understood. Studies using stroke-prone spontaneously hypertensive rats (SHRSPs) suggest that cerebral vascular structure plays an important role in the pathogenesis of cerebral ischemia. SHRSPs have larger cerebral infarcts when ischemia is induced by middle cerebral artery (MCA) occlusion than their normotensive counterparts, the Wistar Kyoto rats. 1,2 This difference appears to be because of remodeling of the cerebral vessels that results in the vessels having a smaller lumen diameter and an impaired ability to dilate in response to ischemia. [3][4][5] It is becoming increasingly clear that aldosterone is involved in the pathophysiology of cardiovascular disease. 6 We have shown previously that chronic treatment of SHRSPs with spironolactone, the aldosterone antagonist, reduces the ischemic cerebral infarct size after MCA occlus...

show abstract

Intracranial Aneurysm and Hemorrhagic Stroke in Glucocorticoid-remediable Aldosteronism

Cited by 176 publications

References 29 publications

Genetics of arterial hypertension and hypotension

Genetics of arterial hypertension and hypotension

Is random screening of value in detecting glucocorticoid-remediable aldosteronism within a hypertensive population?

Mineralocorticoid Receptor Activation Causes Cerebral Vessel Remodeling and Exacerbates the Damage Caused by Cerebral Ischemia

Contact Info

Product

Resources

About