Administration Of Mineralocorticoid Receptor Antagonist Research Articles

Real-world effectiveness of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: a retrospective, non-interventional cohort analysis

Background and purpose: Mineralocorticoid receptor antagonists (MRAs) have been shown in clinical trials to improve outcomes in heart failure with reduced ejection fraction (HFrEF). Yet, it is still uncertain how effective they are in real-world patients with HFrEF. This study aimed to investigate the association between MRAs and outcomes in the overall population and a propensity score-matched cohort, based on patient-level data from the Swedish Heart Failure Registry (SwedeHF). Methods: Patients diagnosed with HFrEF were included from the SwedeHF spanning from 2003 to 2020. Enrollment was based on medication dispensation within 3 months before and 6 months after the index date recorded in the register. Endpoints included all-cause mortality, cardiovascular death, and hospital re-admissions, tracked from the index date until censoring or occurrence of an event. Results: Of 47,103 patients identified through the SwedeHF with HFrEF, 22,368 individuals were not treated with MRA (referred to as MRA naive patients), 21,893 were treated with MRA at a dosage of 25 mg, and 1,423 were treated with MRA at 50 mg once daily. In the overall cohort, the administration of MRA at 25 mg was associated with modest reductions in the risk of all-cause mortality (hazard ratio: 0.92 [0.89–0.95], P < 0.0001) and cardiovascular death (hazard ratio: 0.93 [0.89–0.98], P < 0.01) compared to the MRA naive group. However, both dosages of MRA (25 and 50 mg) were associated with a slight increase in the risk of hospital re-admissions due to heart failure 10% compared to MRA naive patients. These findings were consistent when examining a propensity score-matched cohort. Interaction analysis showed a significantly improved survival rate for patients receiving MRA at 25 mg compared to MRA naive individuals, particularly among those with an estimated glomerular rate ≥30 mL/min/1.73 m2 across all patients and in those aged 70 years and above. Conclusions: The administration of MRA treatment at 25 mg once daily was linked to a modestly improved survival in a real-life HFrEF population, with even more pronounced benefits observed within a specific subgroup. This finding highlights the importance of personalized medicine in providing customized therapeutic advantages.

Serum aldosterone in right ventricular failure versus left ventricular failure before and after mineralocorticoid receptor antagonists: case-control clinical trial

Background Heart failure (HF) is a global growing health threat. This case-control clinical trial aimed to detect the predictive value and difference in aldosterone level between right side heart failure, heart failure with decreased ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) and compare the efficacy and safety of adding mineralocorticoid receptor antagonist (MRA) for treatment. Patients and methods We recruited 151 participants, 135 HF patients divided equally into 45 patients in each group:(1) right side HF (2) HFrEF and (3) HFpEF and 16 healthy controls. Serum aldosterone, troponin and echocardiography were evaluated at the beginning of the study, three and six months after administration of MRA. Results Aldosterone level was significantly greater in HF patients relative to controls. Aldosterone level can detect HF with excellent accuracy. There were significantly lower levels of aldosterone in right side HF compared to left side HF. There was a significant decrease in right ventricle dimensions, pulmonary artery systolic pressure and pulmonary artery size and significant increase in tricuspid annular plane systolic excursion after treatment in patients with right side HF. In the HFrEF group, there was a significant decrease in left ventricular end diastolic dimension and a significant increase in left ventricular EF after treatment. In the HFpEF group, there was a significant decrease in E/A and E/e′ after treatment. Conclusions Aldosterone may have pathogenic role in HF. Measuring and follow-up of aldosterone levels should be considered in HF patients. MRA treatment gives a significant improvement in right side HF group.

Physicians' adherence to the guidelines on the chronic heart failure diagnosis and treatment

Aim To evaluate the physician's knowledge of basic provisions of clinical guidelines for diagnosis and treatment of chronic heart failure (CHF) and to determine how the actions of physicians in their everyday clinical practice comply with these provisions.Materials and methods The study analyzed anonymous questionnaires of 185 physicians (127 cardiologists, 40 internists and general practitioners, 18 other specialists) who were trained in advanced training programs during the 2020/2021 academic year. The main part of the questionnaire included 15 questions related to the classification, diagnosis, pharmacotherapy, and the use of implantable devices in the treatment of patients with CHF.Results The results showed that internists were less than cardiologists aware of major provisions of clinical guidelines for diagnosis and treatment of CHF. However, the knowledge of cardiologists could not be considered sufficient either. 57.5% of internists and 30% of cardiologists incorrectly indicated the main echocardiographic criterion for diagnosis of CHF with reduced left ventricular ejection fraction (CHFrEF). More than 40% of internists did not consider fluid retention with development of the congestion syndrome as a mandatory condition for administration of a loop diuretic to a patient with CHFrEF. 34.6% of cardiologists and 25% of internists correctly determined the indication for the administration of mineralocorticoid receptor antagonists. 37.6% of internists and 21.1% of cardiologists incorrectly indicated the dose of spironolactone recommended for achieving the neuromodulation effect. In determining doses of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers, after arriving at which it is necessary to stop their up-titration, most of the physicians preferred to be based on systolic blood pressure (SBP) rather than on symptoms of hypotension. However, among therapists there were doctors for whom the patient's well-being and clinical symptoms, and not the level of SBP, were priority factors for choosing the tactics of the treatment with ACE inhibitors and beta-blockers. Physicians of both specialties were poorly familiar with indications for cardioverter defibrillator implantation; only 14.2% of cardiologists and 5% of internists chose the correct wording of indications.Conclusion The insufficient knowledge should be considered the basis for the low adherence of doctors to guidelines for diagnosis and treatment of CHF. When developing programs for advanced training of physicians in CHF, special attention should be paid to the use of renin-angiotensin-aldosterone system inhibitors and beta-blockers with detailed discussion of the dosing principles as well as of indications for implantation and results of using cardioverter defibrillators.

FC074: Mineralocorticoid Receptor Drives Parietal Epithelial Cell Activation and Glomerular Injury During Crescentic Glomerulonephritis

Abstract BACKGROUND AND AIMS We have recently demonstrated that targeting specific pathways in parietal epithelial cells (PEC) can markedly alleviate experimental extracapillary glomerular injury (1). Accumulating evidence has indicated the potential contributions of aldosterone and mineralocorticoid receptor (MR) to the pathophysiology of chronic kidney disease. MR is strongly expressed in endothelial cells, glomerular mesangial cells, podocytes and distal tubular cells. Previous studies have shown that administration of mineralocorticoid receptor antagonists, including spironolactone and eplerenone, has beneficial effects in various renal injury animal models, such as unilateral ureteral obstruction, ischemia-reperfusion, cyclosporine-induced nephrotoxicity and hypertensive renal injury. The role of the MR in extra capillary glomerulopathies is still elusive and mechanistically unclear. METHOD To investigate the cell-specific role of the MR in PEC in the course of crescentic glomerulonephritis, we generated chimeric mice specifically lacking MR (Pec Cre Nr3c2lox/lox) in PECs using an inducible Cre recombinase system. Crescentic glomerulonephritis (GN) was induced using the antiglomerular basement membrane nephrotoxic serum (NTS) model. In vivo, biological parameters (albuminuria, blood urea nitrogen—BUN), glomerular injury, as well as PEC activation (CD44, CD9 and fibronectin staining) were assessed. RESULTS At baseline, Pec Cre Nr3c2wt/wt and Pec Cre Nr3c2lox/lox mice displayed no kidney morphology and function differences. When challenged using the NTS model, Pec Cre Nr3c2lox/lox mice showed less albuminuria and preserved renal function as compared to Pec Cre Nr3c2 wt/wt counterparts. Crescents were also more numerous and organized in Pec Cre Nr3c2wt/wt mice. Next, we examined whether pharmacological MR inhibition could alleviate the severity of crescentic GN. When Pec Cre Nr3c2wt/wt mice were orally given eplerenone for 14 days after the onset of the crescentic GN, they were significantly protected from renal injury and failure (decreased proteinuria, normal BUN and reduced number of crescent). Such global action was associated with less activation molecule CD44 on PECs. Thus, genetic disruption of MR in PEC as well as pharmacological inhibition using eplerenone reduced glomerular expression of CD44 and crescent formation. Furthermore, kidney biopsies of individuals diagnosed with crescentic glomerulonephritis displayed increased expression of MR in PEC and crescents. CONCLUSION Altogether, these results indicate the critical role of MR in PEC activation during crescentic glomerulonephritis along with the recently discovered CD9/EGFR/PDGFR pathway. This further supports the idea that the PEC phenotype switch is not a bystander event but plays a targetable critical active pathogenic role in crescentic GN. MR modulation using eplerenone may be a new therapeutic option for the management of such severe disease.

Aldosterone Blockade in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.

Background A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking. Objective To summarize the evidence on the efficacy and safety of MRA in patients admitted for AMI. Methods Articles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021), and ClinicalTrials.gov databases from their inception to December 31, 2020. Results 15 articles with a total of 11,861 patients were included. MRA reduced the risk of all-cause mortality by 16% (relative ratio (RR): 0.84; 95% confidence interval (CI) (0.76, 0.94); P = 0.002) and the incidence of cardiovascular adverse events by 12% (RR: 0.88, 95% CI (0.83, 0.93), P < 0.00001) in post-AMI patients, and further analysis demonstrated that early administration of MRA within 7 days after AMI resulted in a greater reduction in all-cause mortality (RR: 0.72, 95% CI (0.61, 0.85), P < 0.0001). Subgroup analyses showed that post-STEMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA had a 36% reduction in all-cause mortality (RR: 0.64, 95% CI (0.46, 0.89), P = 0.007) and a 22% reduction in cardiovascular adverse events (RR: 0.78, 95% CI (0.67, 0.91), P = 0.002). Meanwhile, post-STEMI patients without LVSD treated with MRA get significant improvements in left ventricular ejection fraction (mean difference (MD): 2.69, 95% CI (2.44, 2.93), P < 0.00001), left ventricular end-systolic index (MD: -4.52 ml/m2, 95% CI (-8.21, -0.83), P = 0.02), and left ventricular end-diastolic diameter (MD: -0.11 cm, 95% CI (-0.22, 0.00), P = 0.05). The corresponding RR were 1.72 (95% CI (1.43, 2.07), P < 0.00001) for considered common adverse events (hyperkalemia, gynecomastia, and renal dysfunction). Conclusions Our findings suggest that MRA treatment reduces all-cause mortality and cardiovascular adverse events in post-AMI patients, which is more significant in patients after STEMI without LVSD. In addition, MRA treatment may exert beneficial effects on the reversal of cardiac remodeling in patients after STEMI without LVSD.

Central Serous Chorioretinopathy - an Overview.

Central serous chorioretinopathy (CSCR) is characterised by retinal serous detachment usually localised in the macular region. CSCR predominantly affects men between 30 and 50years of age. Traditional classification differentiates between acute (duration shorter than 4 to 6 months) and chronic disease (duration longer than 4 to 6 months). The pathogenesis is multifactorial and current thinking assumes the presence of localised choroidal hyperpermeability with subsequent secondary changes in the retinal pigment epithelium (RPE). The symptoms of acute CSCR include central blurred vision, often with deterioration in visual acuity. Optical coherence tomography (OCT) reveals subretinal fluid (SRF) and/or single retinal pigment epithelial detachments. Fluorescein angiography (FA) usually shows a leaking point with absent or only minor RPE changes in the acute phase and indocyanine green angiography (ICG) highlights circumscribed areas of thickened and hyperpermeable choroid. Acute cases may show spontaneous resolution of SRF, but may also recur and/or become chronic. After the initial diagnosis, spontaneous remission is seen in about 70 to 80% of cases, with a recurrence rate of about 50%. Due to the favourable spontaneous course, it is recommended to wait for 4 to 6 months after the first symptoms manifest. Steroid therapy is considered as a major risk factor. Chronic cases are characterised by slow deterioration in visual acuity with reduced contrast and colour perception. There are extensive RPE changes, with secondary degenerative changes of the photoreceptors. The disease can by complicated by choroidal neovascularisation (CNV), especially in elderly patients. The literature lists a number of treatments: The leakage point (visible in the FA) can be treated by focal laser therapy, either micropulse laser or, if sufficiently distant from the fovea, by argon laser coagulation. Randomised trials in chronic CSCR demonstrated good outcomes with photodynamic therapy. With observation periods ranging from 3 to 6 months, several case series reports found improvement after systemic administration of mineralocorticoid receptor antagonists, carbonic anhydrase inhibitors or non-steroidal anti-inflammatory drugs. In the presence of secondary CNV, anti-VEGF treatment should be initiated. It is unclear whether the combination with PDT might be useful.

Prognostic impact of additional mineralocorticoid receptor antagonists in octogenarian heart failure patients.

AimsGuideline‐directed medical therapy (GDMT) including beta‐blockers and renin–angiotensin system inhibitors is shown to reduce mortality risk in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). However, there is little evidence about the efficacy of additional administration of mineralocorticoid receptor antagonists (MRAs) with GDMT in patients ≥80 years presenting with HF. We aimed to investigate the prognostic impact of GDMT with MRA in relation to the age of patients with HF.Methods and resultsThis observational study included patients admitted for HF with reduced LVEF who were discharged alive; among them, 224 patients were ≥80 years, and 661 patients were <80 years. Both populations were divided into three groups depending on whether they received GDMT with or without MRA or single/no GDMT drugs (GDMT+MRA+, GDMT+MRA−, or non‐GDMT, respectively). The primary endpoint was all‐cause mortality. In patients ≥80 years, all‐cause mortality was the lowest in the GDMT+MRA+ group (log‐rank trend, P = 0.034), and no significant differences were observed between the GDMT+MRA− and non‐GDMT groups. Multivariate Cox regression analysis revealed that GDMT+MRA+ was superior to GDMT+MRA−, even after adjusting for parameters at discharge (hazard ratio: 0.32, 95% confidence interval: 0.11–0.99). In patients <80 years, GDMT reduced all‐cause mortality; however, additional MRA was not associated with an improved outcome.ConclusionsThe results of this study suggest that additional MRA to GDMT at discharge is one of the therapeutic options for elderly HF patients with reduced LVEF. This finding is not well documented in previous clinical trials.

Clinical determinants and prognostic implications of renin and aldosterone in patients with symptomatic heart failure.

AimsActivation of the renin–angiotensin–aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF.Methods and resultsWe analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT‐CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all‐cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT‐CHF study, median renin and aldosterone levels were 85.3 (percentile25–75 = 28–247) μIU/mL and 9.4 (percentile25–75 = 4.4–19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted‐HR (95% CI) = 1.47 (1.16–1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted‐HR (95% CI) = 1.16 (0.93–1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT‐CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies.ConclusionsCirculating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the “point” measurement of renin and aldosterone in HF is of limited clinical utility.

Surgery decreases the long-term incident stroke risk in patients with primary aldosteronism

BackgroundHypertension with hyperaldosteronism could be associated with stroke attributable to endothelial injury. Whether the detrimental effect of aldosterone on stroke among primary aldosteronism patients could be mitigated by administration of mineralocorticoid receptor antagonist or by reduction of aldosterone level via adrenalectomy is still inconclusive. MethodsPrimary aldosteronism and essential hypertensive patients were enrolled in the Taiwan National Health Insurance from 1997 to 2009. We used a validated algorithm to enroll primary aldosteronism patients. We conducted a competing risk analysis, using a time-varying Cox proportional hazard model. ResultsWe enrolled 3,167 primary aldosteronism patients with a subgroup of 1,047 aldosterone-producing adenoma patients, and matched these with essential hypertensive controls in a 1:4 ratio. The risk of incident stroke, both ischemic and hemorrhagic, was statistically higher in primary aldosteronism patients than in their essential hypertensive control. The differences in stroke incidences between primary aldosteronism and essential hypertensive patients significantly increased as the hypertensive period lengthened. Primary aldosteronism patients who received mineralocorticoid receptor antagonist treatment had higher risk of all stroke (competing hazard ratio = 1.83, P < .001) compared with their essential hypertensive controls. In light of this, aldosterone-producing adenoma patients had a lower risk of incident stroke after adrenalectomy (competing for hazard ratio = 0.75), but a higher cumulative risk of incident stroke after mineralocorticoid receptor antagonist only (competing for hazard ratio = 1.76) than their matched essential hypertensive patients. ConclusionWe observed an increased stroke risk among primary aldosteronism patients than among their matched essential hypertensive controls. A prolonged duration of hypertension was proportionate to the raised risk of stroke. Our findings emphasize the importance of aldosterone-producing adenoma benefitting from adrenalectomy in attenuating the cerebrovascular event.

O11-3 - Early Administration of Mineralocorticoid Receptor Antagonist Is Useful for Cardiac Reverse Remodeling in Asymptomatic Patients with Dilated Cardiomyopathy

Background: Cardiac reverse remodeling (CRR) is considered to be one of surrogate markers of favorable prognosis in dilated cardiomyopathy (DCM). The administration of mineralocorticoid receptor antagonist (MRA) with ACE inhibitor and beta blocker is recommended to reduce future cardiac events in all symptomatic heart failure patients with reduced ejection fraction. However, little is known about the efficacy of MRA for asymptomatic heart failure patients. We aimed to investigate the association between early administration of MRA and CRR in asymptomatic DCM patients. Methods: We enrolled 74 DCM patients classified as NYHA I in this retrospective cohort study. All patients were divided into two groups; MRA(+) group (n = 33) and MRA(-) group (n = 41). CRR was defined as an absolute increase in left ventricular ejection fraction ≧10% accompanied by a decrease in left ventricular end-diastolic diameter >10% as assessed by echocardiography at 12 months. Results: As for baseline characteristics, the mean of left ventricular ejection fraction and end-diastolic diameter was 36% and 61 mm, respectively. The administration rate of ACE inhibitors/ARBs and was 82% and 81%. Thirty-three (45%) patients were treated with MRA. The rate of CRR was significantly higher in MRA(+) group than in MRA(-) group (58% vs 27%, P = .007). Conclusions: Early administration of MRA is useful for CRR in asymptomatic NYHA I patients with DCM, which may potentially result in a good prognosis.

P3372Is the administration of mineralocorticoid receptor antagonist required in asymptomatic AHA/ACC stage B heart failure patients?

P3372Is the administration of mineralocorticoid receptor antagonist required in asymptomatic AHA/ACC stage B heart failure patients?

Effects of mineralocorticoid receptor antagonists in patients with hypertension and diabetes mellitus: a systematic review and meta-analysis.

Blood pressure (BP) control is important to ameliorate cardiovascular events in patients with diabetes mellitus (DM). However, achieving the target BP with a single drug is often difficult. The objective of this study was to evaluate the antihypertensive effects of mineralocorticoid receptor antagonists (MRAs) as add-on therapy to renin–angiotensin system (RAS) inhibitor(s) in patients with hypertension and DM. Studies were searched through October 2014 in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials. Randomized, controlled trials or prospective, observational studies regarding concomitant administration of MRA and RAS inhibitor(s) in patients with DM were included. Articles were excluded if the mean systolic BP (SBP) was <130 mm Hg before randomization for interventional studies or at baseline for prospective cohort studies. We identified nine eligible studies (486 patients): five randomized placebo-controlled trials; three randomized active drug-controlled trials; and one single-arm observational study. The mean differences in office SBP and diastolic BP (DBP) between the MRA and placebo groups were −9.4 (95% confidence interval (CI) −12.9 to −5.9) and −3.8 (95% CI, −5.5 to −2.2) mm Hg, respectively. Subgroup analysis results for study type, age, baseline office SBP and follow-up duration were similar to those of the main analysis. MRA mildly increased serum potassium (0.4 mEq l−1; 95% CI, 0.3–0.5 mEq l−1). A consistent reduction of albuminuria across these studies was also demonstrated. MRA further reduced SBP and DBP in patients with hypertension and DM already taking RAS inhibitors. Serum potassium levels should be monitored to prevent hyperkalemia.

Mineralocorticoid receptor antagonists and renal involvement in primary aldosteronism: opening of a new era

Primary aldosteronism (PA) is one of the commonest forms of curable hypertension, and use of the plasma aldosterone-to-renin ratio as a screening test has led to a more efficient identification of this condition. Both animal and human studies have indicated that PA is associated with a variety of cardiovascular and renal complications that reflect the capability of elevated aldosterone to induce tissue damage exceeding that induced by hypertension itself. Involvement of the kidney in PA is highly relevant because structural renal damage is associated with less favorable outcome, both in terms of blood pressure response to treatment and possibility to develop progressive renal failure. However, early involvement of the kidney in PA is characterized by functional changes that are largely reversible with treatment. Unilateral adrenalectomy or administration of mineralocorticoid receptor antagonists are the current options for treating an aldosterone-producing adenoma or idiopathic adrenal hyperplasia. Both treatments are effective in correcting hypertension and hypokalemia, and currently available information on their capability to prevent deterioration of renal function indicates that both surgery and medical treatment are of considerable value.

Aldosterone Acting Through the Central Nervous System Sensitizes Angiotensin II-Induced Hypertension

Previous studies have shown that preconditioning rats with a nonpressor dose of angiotensin II (Ang II) sensitizes the pressor response produced by later treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can modulate each other’s pressor effects through actions involving the central nervous system. The current studies tested whether Aldo can cross-sensitize the pressor actions of Ang II to enhance hypertension by employing an induction–delay–expression experimental design. Male rats were implanted for telemetered blood pressure recording. During induction, subpressor doses of either subcutaneous or intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for 1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang II was given subcutaneously for 2 weeks (expression). During induction and delay, Aldo had no sustained effect on blood pressure. However, during expression, Ang II-induced hypertension was greater in the groups receiving subcutaneous or intracerebroventricular Aldo during induction in comparison with those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of delay and expression showed increased mRNA expression of several renin–angiotensin–aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca 2+ ] i after Ang II treatment, and there was a greater Fra-like immunoreactivity present at the end of expression in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of Ang II-induced hypertension probably by mechanisms that involve the central nervous system.

Aldosterone and the cardiovascular system: a dangerous association.

Initial studies have focussed on the actions of aldosterone in renal electrolyte handling and, as a consequence, blood pressure control. More recently, attention has primarily been focussed on its actions on the heart and vascular system, where it is locally produced. Aldosterone by binding mineralocorticoid receptors causes oxidative stress, fibrosis and triggers an inflammatory response in the cardiovascular system. All these effects could be underlying the role of aldo-sterone on cardiac and vascular remodelling associated with different pathological situations. At the vascular level, aldo-sterone affects endothelial function because administration of aldosterone to rats impaired endothelium-dependent relaxations. In addition, the administration of mineralocorticoid receptor antagonists ameliorates endothelium-dependent relaxation in models of both hypertension and atherosclerosis, and in patients with heart failure. Several mechanisms can participate in this effect, including production of vasoconstrictor factors and a reduction in nitric oxide levels. This reduction can involve both a decrease in its production as well as an increase in its degradation by reactive oxygen species. Aldosterone can produce oxidative stress by the activation of transcription factors such as the NF-κB system, which can also trigger an inflammatory process through the production of different cytokines. At cardiac level, high levels of aldosterone can also adversely impact heart function by producing cardiac hypertrophy, diastolic dysfunction and electrical remodelling through changes in ionic channels. All these effects can explain the beneficial effect of mineralocorticoid blockade in the cardiovascular system.

Aldosterone and the vascular system

Aldosterone can act in different tissues exerting physiological and pathological effects. At the vascular level, aldosterone affects endothelial function since administration of aldosterone impaired endothelium-dependent relaxations. In addition, the administration of mineralocorticoid receptor antagonists ameliorate relaxation to acetylcholine in models of both hypertension and atherosclerosis and in patients with heart failure. A reduction in nitric oxide levels seems to be the main mechanism underlying this effect due to a reduction in its production as well as an increase in its degradation by reactive oxygen species. Aldosterone is a pro-inflammatory factor that can participate in the vascular inflammatory process associated with different pathologies including hypertension through activation of the NFκB system, which mediates the vascular production of different cytokines. This mineralocorticoid also participates in the vascular remodeling observed in hypertensive rats since the administration of eplerenone improved the media-to-lumen ratio in these animals. This effect seems to be due to an increase in extracellular matrix. In summary, aldosterone through mineralocorticoid receptors can participate in the vascular damage associated with different pathologies including hypertension through its prooxidant, pro-inflammatory and profibrotic effects that triggered endothelial dysfunction, an inflammatory process and vascular remodeling.