317 Aldosterone and interleukin-6: the synergic effect in COVID-19

Aims Several evidence have identified the role of Interleukin-6 (IL-6) in the cytokine storm induced by COVID-19. Interestingly, the correlation between the serum levels of IL-6 and the plasma aldosterone has already been demonstrated in patients affected by primary aldosteronism (PA). Thus, we suppose that hyperaldosteronism may increase IL-6 levels in COVID-19. Methods and results We report a case of 47-year-old female Covid-19 patient who had developed severe pneumonia complicated by Guillain–Barreé syndrome (GBS). Blood test revealed high levels of IL-6 (serum IL-6: 402 pg/ml) and of its soluble receptor (soluble IL-6 receptor >1900 pg/ml) and she required mechanical ventilation for severe hypoxaemia. Furthermore, the evidence of right adrenal adenoma, resistant hypertension, severe hypokalaemia, and high serum levels of aldosterone with high aldosterone/renin ratio were also consistent with diagnosis of PA. Thus, Spironolactone was administered with rapid improvements in clinical condition. Finally, she was diagnosed with acute motor sensitive neuropathy and started the rehabilitation phase. Conclusions Elevated aldosterone levels in PA may stimulate IL-6 production, inducing more severe forms of COVID-19 with the development of serious complications such as GBS. Hyperaldosteronism may also contribute to the poorest prognosis of patients with secondary aldosteronism such as heart failure and COVID-19, in which elevated IL-6 levels could exert its detrimental effects, mostly on the progression of ventricular dysfunction. Further studies are necessary to evaluate therapy with mineralocorticoid receptors antagonists such as spironolactone in COVID-19.

EVALUATION OF THE CORTICOSTEROID RECEPTORS’ LEVEL IN THE KIDNEYS OF RATS AFTER SYSTEMIC ISCHEMIA-REPERFUSION

Background: With disturbance of the systemic blood supply, the body experiences hypoxia and stress. Under stress of any etiology, there is a non-specific rearrangement of physiological and biochemical processes. These processes occur under the influence of corticosteroid hormones. Aim: To determine the level of corticosteroid receptors in the kidneys of rats at different times after systemic ischemia-reperfusion. Methods: The study included 80 male white rats. All the animals were divided into 2 groups. A model of systemic ischemia-reperfusion was created in the main group (n=70). Further, on 1, 3, 5, 7, 14, 21 and for 35 days, we determined the level of gluco - and mineralocorticoid receptors in the kidneys. Results: In the animals of the main group, we observed a short-term period (during the first 3 days) of a decrease in the content of both glucorticoid (p<0.05) and mineralocorticoid (p<0.01) receptors. The dynamics of recovery of the level of corticosteroid receptors was 3 times faster than that of mineralocorticoid receptors. Conclusions: The dynamics of corticosteroid receptors’ level in the kidneys of rats after ischemia caused by an arrest of systemic circulation show the recovery time after ischemia-reperfusion injury, which ensures the stability of an individual to hypoxia.

Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II: A Randomized Crossover Study

Background Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure‐raising hormone aldosterone. Besides its well‐described renal effects, aldosterone is also believed to have vascular effects, acting through mineralocorticoid receptors present in endothelial and vascular smooth muscle cells, although mineralocorticoid receptors‐independent actions are also thought to be involved. Methods and Results To gain further insight into the effect of increased potassium intake and potassium‐stimulated hyperaldosteronism on the human cardiovascular system, we conducted a randomized placebo‐controlled double‐blind crossover study in 25 healthy normotensive men, where 4 weeks treatment with a potassium supplement (90 mmol/day) was compared with 4 weeks on placebo. At the end of each treatment period, we measured potassium and aldosterone in plasma and performed an angiotensin II (AngII) infusion experiment, during which we assessed the aldosterone response in plasma. Hemodynamics were also monitored during the AngII infusion using ECG, impedance cardiography, finger plethysmography (blood pressure‐monitoring), and Doppler ultrasound. The study showed that higher potassium intake increased plasma potassium (mean±SD, 4.3±0.2 versus 4.0±0.2 mmol/L; P =0.0002) and aldosterone (median [interquartile range], 440 [336–521] versus 237 [173–386] pmol/L; P <0.0001), and based on a linear mixed model for repeated measurements, increased potassium intake potentiated AngII‐stimulated aldosterone secretion ( P =0.0020). In contrast, the hemodynamic responses (blood pressure, total peripheral resistance, cardiac output, and renal artery blood flow) to AngII were similar after potassium and placebo. Conclusions Increased potassium intake potentiates AngII‐stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men. Registration EudraCT Number: 2013‐004460‐66; URL: https://www.ClinicalTrials.gov ; Unique identifier: NCT02380157.

A Literature Review of the Pharmacokinetics, Pharmacodynamics, and Possible Uses of Spironolactone

Spironolactone (SL) is an antimineralocorticoid derived from progesterone, and was therefore developed as a diuretic for hypertension and edema treatment (Kolkhof & Barfacker, 2017). As a prodrug, its effects are largely mediated by its metabolites, 7α-thiomethylspironolactone and canrenone (Janowski et al., 1996), which are ultimately eliminated through the urine (Abshagen et al., 1977). Later on, it was discovered that SL also exhibits moderate antiandrogenic activity due to its structural similarity to progesterone (Menard, 2004), allowing it to be used as an off-label treatment for hyperandrogenism and its associated symptoms, such as hirsutism and acne (Voegli et al., 2009). As researchers continue to elucidate the role of mineralocorticoid receptors in cognition and behaviour, new possibilities for SL as an anxiolytic may also emerge in the future (Otte et al., 2007). With all that being said, SL’s sexual side-effects, especially in males, continue to limit the various applications of this multi-use drug.