Hypokalemia in primary aldosteronism (PA) patients correlates with higher levels of cardiovascular events and altered left ventricular geometry. However, the influence of aldosterone on microvascular endothelial function and the effect of hypokalemia on the vascular structure still remain unclear. We investigated the peripheral arterial functions, including the endothelial function of microvasculature and arterial stiffness in PA and essential hypertension (EH) patients, and the correlation between hypokalemia and peripheral arterial function among PA patients. Twenty patients diagnosed as EH and 37 patients with PA were enrolled in this study. Reactive hyperemia index (RHI) and the augmentation index (AI) were obtained by non-invasive peripheral arterial tonometry. Twenty EH patients and a total of 37 PA patients, including 21 patients with normokalemia and 16 patients with hypokalemia, were enrolled and divided into groups 1, 2 and 3 respectively. PA patients had significantly higher AI (p=0.024) but not RHI than EH patients. RHI showed no difference between groups 1, 2 and 3. Group 3 had higher AI than either group 1 or group 2. In the whole study population, serum potassium level, after multivariate regression analysis testing, was the only factor associated with AI (ß= −0.102; p=0.002). In PA patients, serum potassium level was the only significant factor correlated with AI. (r= −0.458; p=0.004) PA patients had higher arterial stiffness but comparable microvascular endothelial function to EH patients. Hypokalemia correlated with arterial stiffness but not microvascular endothelial function in PA patients.

Excessive aldosterone secretion causes endothelial dysfunction, vascular inflammation, and vascular fibrosis in patients with primary aldosteronism (PA). Endothelial function is closely related to endothelial mitochondria. However, the effects of elevated aldosterone levels on endothelial mitochondria remain unclear. In this study, we used primary cultured human umbilical vein endothelial cells (HUVECs) to investigate the effects of aldosterone on endothelial mitochondria. Mineralocorticoid receptor (MR) small interfering (si)RNA or glucocorticoid receptor (GR) siRNA were used to confirm the pathway by which aldosterone exerts its effects on the mitochondria of HUVECs. The results showed that excess aldosterone suppressed mitochondrial DNA copy numbers, anti-mitochondrial protein, and SOD2 protein expression in a dose- and time-dependent manner. These effects were attenuated by treatment with MR siRNA, but not with GR siRNA. Furthermore, it was attenuated by treatment with a mitochondria-targeted antioxidant (Mito-TEMPO, associated with mitochondrial reactive oxygen species (ROS) production), but not N-acetyl-L-cysteine (associated with cytosolic ROS production), which suggests that the process was through the mitochondrial ROS pathway, but not the cytosolic ROS pathway. In conclusion, aldosterone excess suppressed endothelial mitochondria through the MR/mitochondrial ROS pathway.

Estimated glomerular filtration rate (eGFR) is an important topic in patients with primary aldosteronism (PA). However, the relationship between left ventricular structure and eGFR is unclear. We conducted a prospective, observational, and cross-sectional study to analyze 168 patients with PA and 168 propensity score-matched patients with essential hypertension (EH) as the control group, matched by age, gender, and systolic blood pressure. In the patients with PA, the eGFR was not correlated with left ventricular mass index (LVMI; r=−0.065, p=0.404), while in the patients with EH, the eGFR was negatively correlated with LVMI (r=−0.309, p<0.001). To test whether eGFR had a non-linear relationship with LVMI among the patients with PA, we stratified the patients with PA according to the tertile of eGFR (low, medium, and high tertile). The medium tertile of patients had a significantly lower LVMI than those in the other two tertiles (LVMI: 143.5±41.6, 120.5±40.5, and 133.1±34.3 g/m², from the lowest to highest tertile of eGFR; analysis of covariance p=0.032). The medium tertile of eGFR is associated with lowest LVMI. Patients with PA with high and low eGFR were associated with higher LVMI. The findings implied that the reasons for an increased LVMI in patients with PA may be different to those in patients with EH.