Significance: Vascular oxidative stress and endothelial cell dysfunction contribute to various human pathologies. Here, we show that, in vascular endothelial cells, a key mitochondrial antioxidant enzyme, namely thioredoxin reductase 2 (TrxR2), plays a central role in the control of vascular integrity. Its targeted loss is associated with disruption of both nitric oxide (·NO) and redox homeostasis in vivo. Impaired TrxR2 activity leads to elevated steady-state levels of peroxynitrite, reflecting the decreased bioavailability of ·NO by its O ₂ ^{· −} mediated oxidative inactivation. Thus, TrxR2 represents a central control point of peroxynitrite levels by providing reducing equivalents to mitochondrial peroxiredoxins that, in turn, catalytically reduce peroxynitrite to nitrite. The data additionally support pharmacological approaches for mitochondrial peroxynitrite detoxification under conditions of vascular oxidative stress.

In patients with primary aldosteronism, specific treatment provides prognostic benefit over optimal antihypertensive therapy and is therefore crucial to reduce mortality and morbidity in this subgroup of patients with hypertension. Prognostic relevance has been shown for adrenalectomy in unilateral disease and for medical treatment with mineralocorticoid receptor antagonists in bilateral adrenal hyperplasia. Collectively, evidence points to the superiority of surgical treatment compared to medical treatment. The causal approach of removing the mineralocorticoid excess, as well as the often-accompanying glucocorticoid excess, might provide one biologically plausible explanation for the observation of slightly better outcomes with surgical therapy. However, in patients living with primary aldosteronism, medical treatment is often insufficient for three major reasons. First and foremost, no marker of sufficient aldosterone blockade has yet been established and therefore adequate treatment of the aldosterone excess is often dismissed as a treatment goal. Second, side effects often limit patient compliance. Third, as recommendations differ from other indications like heart failure, drug dosing is often inadequate. The aim of this review is first to provide an overview over medical treatment options and second to review potential markers for treatment surveillance in patients with primary aldosteronism.

Background: Primary aldosteronism (PA) is a frequent cause of hypertension. Aldosterone excess together with high dietary salt intake aggravates cardiovascular damage, despite guideline‐recommended mineralocorticoid receptor antagonist (MRA) treatment.Objectives: To investigate the antihypertensive impact of a moderate dietary salt restriction and associated physiological changes, including mental well‐being.Methods: A total of 41 patients with PA on a stable antihypertensive regimen—including MRA—followed a dietary salt restriction for 12 weeks with structured nutritional training and consolidation by a mobile health app. Salt intake and adherence were monitored every 4 weeks using 24‐h urinary sodium excretion and nutrition protocols. Body composition was assessed by bioimpedance analysis and mental well‐being by validated questionnaires.Results: Dietary salt intake significantly decreased from 9.1 to 5.2 g/d at the end of the study. In parallel, systolic (130 vs. 121 mm Hg) and diastolic blood pressure (BP) (84 vs. 81 mm Hg) improved significantly. Patients’ aptitude of estimating dietary salt content was refined significantly (underestimation by 2.4 vs. 1.4 g/d). Salt restriction entailed a significant weight loss of 1.4 kg, improvement in pulse pressure (46 vs. 40 mm Hg) and normalization of depressive symptoms (PHQD scale, p < 0.05). Salt restriction, cortisol after dexamethasone suppression test and dosage of renin‐angiotensin‐aldosterone‐system (RAAS) blockers were independently associated with BP reduction.Conclusion: A moderate restriction of dietary salt intake in patients with PA substantially reduces BP and depressive symptoms. Moreover, the findings underline that a sufficient RAAS blockade seems to augment the effects of salt restriction on BP and cardiovascular risk.

Rodents exposed to mineralocorticoid excess have considerably decreased taste sensitivity for sodium chloride (NaCl) and show high dietary sodium intake. A similar shift in NaCl taste perception could be detrimental in humans when aldosterone excess in primary aldosteronism (PA) causes hypertension and favors high sodium consumption. To investigate NaCl taste sensitivity in patients with PA, we studied NaCl taste recognition thresholds as measures of NaCl taste sensitivity in forty patients with PA before and after treatment of aldosterone excess. Forty patients with primary hypertension and 40 healthy normotensive volunteers served as controls. In this context, the subjects compared 10 different NaCl solutions (0.5–256 mmol/L) with distilled water. We also assessed individual NaCl intake using self-reported 24-hour recalls and duplicate determinations of sodium excretion in 24-hour urine. Patients with PA showed significantly higher NaCl taste recognition thresholds (median 32 versus 24 mmol/L in primary hypertension, P =0.010, and 16 mmol/l in normotensive control, P <0.001). Following specific treatment for PA, the taste recognition threshold for NaCl significantly improved in patients with unilateral PA undergoing adrenalectomy (median 16 versus 32 mmol/L at baseline, P =0.017) and in patients on MRA (mineralocorticoid receptor antagonists; median 16 versus 32 mmol/L at baseline, P <0.001) but was unaltered in healthy volunteers (median 16 versus 16 mmol/L at baseline, P =0.438). Our data show a significantly impaired NaCl taste perception in patients with PA. Surgical as well as medical treatment of PA significantly improved NaCl taste perception in patients with PA.

Primary aldosteronism is an endocrine disorder caused by excessive production of aldosterone by the adrenal glands, and is recognized as the most important cause of endocrine hypertension. With specific therapy, this type of hypertension is potentially curable. In the general population, high salt intake increases the risk for cardiovascular diseases like stroke. In populations with aldosterone excess, observational and experimental data suggest that aldosterone-induced organ damage requires a combination of high dietary salt intake and high plasma aldosterone, i.e., plasma aldosterone levels inappropriately high for salt status. Therefore, understanding the relationship between plasma aldosterone levels and dietary salt intake and the nature of their combined effects is crucial for developing effective prevention and treatment strategies. In this review, we present an update on findings about primary aldosteronism and salt intake and the underlying mechanisms governing their interaction.

Patients with primary aldosteronism (PA) are at increased cardiovascular risk, compared to patients with essential hypertension (EH). Cardiovascular damage could depend on PA phenotype, potentially being lower in milder forms of PA. Our aim was to assess atherosclerotic burden and arterial stiffness in 88 prospectively recruited patients, including 44 patients with mild PA and EH respectively. All patients underwent a structured study program, including measurements of ankle-brachial index, oscillometric measurement of central pulse wave velocity (cPWV) and vascular ultrasound examination of the supraaortic arteries, the abdominal aorta, and the femoropopliteal arteries. A plaque score was calculated to estimate atherosclerotic burden for each patient. This is a prospective case-control study set at a tertiary care hospital. Patients with PA and EH matched well for age, gender, blood pressure, BMI, and cardiovascular risk factors such as diabetes mellitus and smoking status. Common carotid intima-media thickness (0.77 vs. 0.75 mm; p=0.997) and cPWV (7.2 vs. 7.1 m/s; p=0.372) were comparable between patients with PA and EH. The atherosclerotic burden, as expressed by the plaque score, did not differ between the two groups (p=0.159). However, after initiation of treatment cPWV was significantly decreased in patients with PA (p=0.017). This study shows that subclinical atherosclerotic burden and arterial stiffness in patients with milder forms of PA is comparable to patients with EH. Nevertheless, specific treatment for PA significantly improved cPWV, which argues for a more liberal use of mineralocorticoid receptor antagonists in patients with arterial hypertension.