Effect of Spironolactone in Hypertensive Patients

Crane, Milton G.; Harris, Jennifer

doi:10.1097/00000441-197012000-00001

Cited by 133 publications

(26 citation statements)

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“…The reductions compare favorably with those observed with other drugs used as initial or add-on therapy 20 -23 but are consistent with those observed in smaller uncontrolled studies of spironolactone in essential and resistant hypertension. [3][4][5][6][12][13][14][15] Although the observed reductions are impressive, we cannot be certain that they translated into reductions in cardiovascular outcomes. However, the best available data suggest that the magnitude of BP reduction rather than choice of antihypertensive agent is the most important factor in reducing most major cardiovascular events.…”

Section: Discussionmentioning

confidence: 92%

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Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension

et al. 2007

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Abstract-Spironolactone is recommended as fourth-line therapy for essential hypertension despite few supporting data for this indication. We evaluated the effect among 1411 participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm who received spironolactone mainly as a fourth-line antihypertensive agent for uncontrolled blood pressure and who had valid BP measurements before and during spironolactone treatment. Among those who received spironolactone, the mean age was 63 years (SD: Ϯ8 years), 77% were men, and 40% had diabetes. Spironolactone was initiated a median of 3.2 years (interquartile range: 2.0 to 4.4 years) after randomization and added to a mean of 2.9 (SD: Ϯ0.9) other antihypertensive drugs. The median duration of spironolactone treatment was 1.3 years (interquartile range: 0.6 to 2.6 years). The median dose of spironolactone was 25 mg (interquartile range: 25 to 50 mg) at both the start and end of the observation period. During spironolactone therapy, mean blood pressure fell from 156.9/85.3 mm Hg (SD: Ϯ18.0/11.5 mm Hg) by 21.9/9.5 mm Hg (95% CI: 20.8 to 23.0/9.0 to 10.1 mm Hg; PϽ0.001); the BP reduction was largely unaffected by age, sex, smoking, and diabetic status. Spironolactone was generally well tolerated; 6% of participants discontinued the drug because of adverse effects. The most frequent adverse events were gynecomastia or breast discomfort and biochemical abnormalities (principally hyperkaliemia), which were recorded as adverse events in 6% and 2% of participants, respectively. In conclusion, spironolactone effectively lowers blood pressure in patients with hypertension uncontrolled by a mean of Ϸ3 other drugs. Although nonrandomized and not placebo controlled, these data support the use of spironolactone in uncontrolled hypertension.

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Section: Discussionmentioning

confidence: 92%

“…[3][4][5][6][7][8][9][10][11] Small uncontrolled studies have also demonstrated its effectiveness in patients with resistant hypertension. [12][13][14][15] This is reflected in the latest British Hypertension Society guidelines, which recommend spironolactone as fourth-line therapy when other drugs have failed to control BP.…”

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confidence: 99%

Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension

et al. 2007

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“…This hypothesis has received further support from reports that in low-renin essential hypertension, the elevated blood pressure is "volume-dependent" and responds to diuretic therapy more readily thain other forms of essential hypertension (8,10,13,14). That adrenal factors may be involved in this syndrome is further suggested by the findings that blockade of aldosterone biosynthesis by aminogluthetimide (15) or of the action of sodium-retaining steroids by spironolactone (8,(9)(10)(11)(13)(14)(15) restilts in greater amelioration of the hypertension in patients witlh low renin as compared to those witlh normal renin levels.…”

Section: Introductionmentioning

confidence: 97%

Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.

Baxter¹,

Schambelan²,

Matulich³

et al. 1976

J. Clin. Invest.

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A B S T R A C T Aldosterone receptors from rat kidney slices were utilized in a competitive binding technique to analyze the contribution of various steroids to plasma "mineralocorticoid" activity and to assess their possible role in hypertension. To consider simultaneously the plasma binding, steroids were incubated with slices in undiluted plasma; competitor activities for [3H]aldosterone binding were aldosterone, 100%; deoxycorticosterone, 16.2%; cortisol, 0.4%; and 18-hydroxy-deoxycorticosterone and 18-hydroxy-corticosterone, 0.1%. These steroids were more active in buffer than plasma, suggesting that they bind to plasma and that this reduces their receptor binding. Analysis of the competition data suggests that at normal plasma concentrations, aldosterone occupies the receptors to a major extent, cortisol occupies some of the receptors, and deoxycorticosterone and 18-hydroxydeoxycorticosterone contribute little to receptor occupancy. Two steroids implicated in low-renin essential hypertension, 16i#-hydroxy-dehydroepiandrosterone and 16-oxoandrostenediol, did not have significant competitor activity.Competitor activity in plasmas from normal subjects taken at 12 noon (upright) was greater than that in those taken at 8 a.m. (supine). Since the 12 noon samThis work has been published in abstract form: 1975.

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“…Whether or not other characteristics of a hypermineralocorticoid state, such as increased exchangeable sodium and extracellular fluid, exist is controversial (Jose et al, 1970;Woods et al, 1969;Lebel et al, 1974;Schalekamp et al, 1974). The specificity of spironolactone in correcting the hypertension in this hormonally defined hypertensive group again is questionable (Crane & Harris, 1970;Vaughan et al, 1973;Carey et a/., 1972). Although there is compelling evidence against an MCH, there is no evidence against the existence of a steroid that causes hypertension.…”

Section: N O R M a L Aldosterone Productionmentioning

confidence: 99%

A Perspective on Aldosterone Abnormalities

Biglieri

1976

Clinical Endocrinology

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Not all the varied clinical disorders in which aldosterone and the mineralocorticoid hormones are involved have been reviewed. Only those disorders in which the mineralocorticoid hormones and their regulatory factors are the principal cause of the biochemical and clinical abnormalities have been examined. These are many and varied. Appreciation of the extent and magnitude of their involvement in the regulation of blood pressure, body fluids, and electrolyte composition continues to grow.The major direct clinical impact of the mineralocorticoid hormones appears to be in two areas: hypertension and potassium homeostasis. Their part in the mosaic of hypertension is established in primary hyperaldosteronism, but they also appear to affect and modify the hypertensive process in primary or essential hypertension. The probe continues.Hypoaldosteronism is more than the rare occurrence associated with Addison's disease. It may be the clue to the presence of nonaldosterone mineralocorticoid excess syndromes, and is obviously of critical importance in an increasing number of patients with chronic renal failure of varied aetiologies.The principal mineralocorticoid hormones (MCHs) of the adrenal cortex are deoxycorticosterone (DOC) and aldosterone. Deoxycorticosterone at normal levels binds to corticosteroid-binding globulin and has weak sodium-retaining and potassium-secreting properties and therefore contributes little to total mineralocorticoid activity, whereas aldosterone is free of binding and thus is physiologically the more potent MCH.Abnormalities in sodium and potassium metabolism, volume regulation, and blood pressure are the clinical conditions in which disorders of aldosterone secretions are thought to have a role. In this article, alterations of aldosterone production in disorders of blood pressure and potassium metabolism will be discussed.

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Effect of Spironolactone in Hypertensive Patients

Cited by 133 publications

References 0 publications

Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension

Effect of Spironolactone on Blood Pressure in Subjects With Resistant Hypertension

Aldosterone receptors and the evaluation of plasma mineralocorticoid activity in normal and hypertensive states.

A Perspective on Aldosterone Abnormalities

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