Rise in Plasma Concentration of Aldosterone During Long-Term Angiotensin Ii Suppression

Staessen, Jan A.; Lijnen, Paul; Fagard, Robert; Verschueren, L J; Améry, A

doi:10.1677/joe.0.0910457

Cited by 299 publications

(156 citation statements)

References 31 publications

(52 reference statements)

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“…1 Although ACE-I might be expected to reduce aldosterone levels by reducing the stimulating effect of angiotensin II on aldosterone production, recent studies have demonstrated that neither angiotensin II nor aldosterone plasma levels are suppressed chronically by clinically prescribed doses of ACE-I. 2,3 Aldosterone has been implicated as a contributor to structural remodeling of the left ventricle, 4 -6 and the beneficial effects of spironolactone on mortality have been attributed to inhibition of the collagen-generating influence of aldosterone. 7,8 Aldosterone secretion is stimulated by several factors in addition to angiotensin II, and these alternate mechanisms may be important determinants of aldosterone production and its levels in the plasma and tissues in patients with HF.…”

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confidence: 99%

Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

et al. 2003

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MD; for the Valsartan Heart Failure Trial InvestigatorsBackground-Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure. Methods and Results-Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150Ϯ160 pg/mL, meanϮSD; nϭ2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137Ϯ124 pg/mL, meanϮSD; nϭ2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8Ϯ3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8Ϯ3.0 pg/mL (SEM) (Ϫ17.4%) in the valsartan group (PϽ0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor ␤-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs. Conclusions-Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure. Key Words: heart failure Ⅲ angiotensin Ⅲ trials D espite the remarkable success of ACE inhibitors (ACE-I) in reducing the mortality and morbidity from heart failure (HF), the addition of the aldosterone inhibitor spironolactone was shown to cause an additional 30% decrease in mortality in the Randomized Aldactone Evaluation Study (RALES). 1 Although ACE-I might be expected to reduce aldosterone levels by reducing the stimulating effect of angiotensin II on aldosterone production, recent studies have demonstrated that neither angiotensin II nor aldosterone plasma levels are suppressed chronically by clinically prescribed doses of ACE-I. 2,3 Aldosterone has been implicated as a contributor to structural remodeling of the left ventricle, 4 -6 and the beneficial effects of spironolactone on mortality have been attributed to inhibition of the collagen-generating influence of aldosterone. 7,8 Aldosterone secretion is stimulated by several factors in addition to angiotensin II, and these alternate mechanisms may be important determinants of aldosterone production and its levels in the plasma and tissues in patients with HF. In...

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Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

et al. 2003

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“…[20][21][22] ALD breakthrough generally occurs in about half of the cases within 12 months. 23,24 Recently, ALD breakthrough was observed in 23% of hypertensive patients during candesartan treatment.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

et al. 2009

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In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB. A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n¼25): continuous candesartan treatment at a stable dose; and olmesartan group (n¼25): candesartan (8 mg day À1 ) was changed to olmesartan given at a dose of 20 mg day À1 . There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135 ± 36 vs. 123 ± 29 g m À2 ; Po0.01). These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.

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“…This unfortunately is not the case. Several investigators have demonstrated that the use of ACEinhibitors initially causes an acute decrease in the concentration of aldosterone, but with continued use, this suppression is not sustained (59)(60)(61)(62).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Aldosterone as a Mediator of Progressive Renal Dysfunction: Evolving Perspectives.

Epstein

2001

Intern. Med.

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End-stage renal disease (ESRD)comprises an enormous public health burden, with an incidence and prevalence that are increasingly on the rise. This escalating prevalence suggests that newer therapeutic interventions and strategies are neededto complement current therapeutic approaches. Although much evidence demonstrates conclusively that angiotensin II mediates progressive renal disease, recent evidence also implicates aldosterone as an important pathogenetic factor in progressive renal disease. Recently, several lines of experimental evidence demonstrate that selective blockade of aldosterone, independent of renin-angiotensin blockade, reduces proteinuria and nephrosclerosis in the spontaneously hypertensive stroke-prone rat (SHRSP) model and reduces proteinuria and glomerulosclerosis in the subtotally nephrectomized rat model (ie, remnant kidney). Whereas pharmacologic blockade with angiotensin II receptor blockers and angiotensin-converting enzyme (ACE)inhibitors reduces proteinuria and nephrosclerosis/glomerulosclerosis, selective rein fusion of aldosterone restores these abnormalities despite continued renin-angiotensin blockade. Aldosterone may promote fibrosis by several mechanisms, including plasminogen activator inhibitor-1 (PAI-1) expression and consequent alterations of vascular fibrinolysis, by stimulation of transforming growth factor-betal , and by stimulation of reactive oxygen species (ROS). Based on this formulation, randomized clinical studies will be initiated to delineate the potential renal-protective effects of aldosterone receptor blockade. (Internal Medicine 40: 573-583, 2001) Keywords: aldosterone receptor antagonist, renin-angiotensin system, end-stage renal disease (ESRD), diabetic nephropathy, plasminogen activator inhibitor-1 (PAI-1)

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Rise in Plasma Concentration of Aldosterone During Long-Term Angiotensin Ii Suppression

Cited by 299 publications

References 31 publications

Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

Aldosterone as a Mediator of Progressive Renal Dysfunction: Evolving Perspectives.

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