Chronic activation of ß-adrenergic receptors leads to tissue water and electrolyte retention.

Beta-adrenergic receptors (ß-AR) are expressed on the membranes of various cell types and their activation affects body water balance by modulating renal sodium and water excretion, cardiovascular function and metabolic processes. However, ß-AR-associated body fluid imbalance has not been well characterised. In the present study, we hypothesized that chronic ß-AR stimulation increases electrolyte and water content at the tissue level. We evaluated the effects of isoproterenol, a non-selective ß-AR agonist, on electrolyte and water balance at the tissue level. Continuous isoproterenol administration for 14 days induced cardiac hypertrophy, associated with sodium-driven water retention in the heart, increased the total body sodium, potassium and water contents at the tissue level, and increased the water intake and blood pressure of the mice. There was greater urine output in response to the isoproterenol-induced body water retention. These isoproterenol-induced changes were reduced by propranolol, a non-selective beta-receptor inhibitor. Isoproterenol-treated mice even without excessive water intake had higher total body electrolyte and water contents, and this tissue water retention was associated with lower dry body mass, suggesting that ß-AR stimulation in the absence of excess water intake induces catabolism and water retention. These findings suggest that ß-AR activation induces tissue sodium and potassium retention, leading to body fluid retention, with or without excess water intake. This characterisation of ß-AR-induced electrolyte and fluid abnormalities improves our understanding of the pharmacological effects of ß-AR inhibitors. Significance Statement We have shown that chronic ß-AR stimulation causes cardiac hypertrophy associated with sodium-driven water retention in the heart and increases the accumulation of body sodium, potassium and water at the tissue level. This characterisation of the ß-AR-induced abnormalities in electrolyte and water balance at the tissue level improves our understanding of the roles of ß-AR in physiology and pathophysiology and the pharmacological effects of ß-AR inhibitors.

COVID-19 fatality and DALYs, and associated metabolic disorders and ambient air pollutants in pre-Omicron era of the pandemic: an international comparative study.

BACKGROUND: Air pollution and a number of metabolic disorders have been reported to increase the risk of severe COVID-19 outcomes. This study explored the association between severe COVID-19 outcomes, metabolic disorders and environmental air pollutants, at regional level, across 38 countries. METHODS: We conducted an ecological study using COVID-19 data related to countries of the Organization for Economic Cooperation and Development (OECD), with an estimated population of 1.4 billion. They were divided into 3 regions: 1. Europe & Middle east; 2. Americas (north, central & south America); 3. East-Asia & West Pacific. The outcome variables were: COVID-19 case-fatality rate (CFR) and disability-adjusted life years (DALYs) at regional level. Freely accessible datasets related to regional DALYs, demographics and other environmental pollutants were obtained from OECD, WHO and the World in Data websites. Generalized linear model (GLM) was performed to determine the regional determinants of COVID-19 CFR and DALYs using the aggregate epidemiologic data (Dec. 2019-Dec. 2021). RESULTS: Overall cumulative deaths were 65,000 per million, for mean CFR and DALYs of 1.31 (1.2)% and 17.35 (2.3) years, respectively. Globally, GLM analysis with adjustment for elderly population rate, showed that COVID-19 CFR was positively associated with atmospheric PM2.5 level (beta = 0.64(0.0), 95%CI: 0.06-1.35; p < 0.05), diabetes prevalence (beta = 0.26(0.1), 95%CI: 0.12-0.41; p < 0.001). For COVID-19 DALYs, positive associations were observed with atmospheric NOx level (beta = 0.06(0.0), 95%CI: 0.02-0.82; p < 0.05) and diabetes prevalence (beta = 0.32(0.2), 95%CI: 0.04-0.69; p < 0.05). At regional level, adjusted GLM analysis showed that COVID-19 CFR was associated with atmospheric PM2.5 level in the Americas and East-Asia & Western Pacific region; it was associated with diabetes prevalence for countries of Europe & Middle east and East-Asia & Western Pacific region. Furthermore, COVID-19 DALYs were positively associated with atmospheric PM2.5 and diabetes prevalence for countries of the Americas only. CONCLUSION: These findings confirm that diabetes and air pollution increase the risk of disability and fatality due to COVID-19, with disparities in terms of their impact. They suggest that efficient preventive and management programs for diabetes and air pollution countermeasures would have curtailed severe COVID-19 outcome rates.

Effects of D-allose on ATP production and cell viability in neonatal rat cardiomyocytes.

2-Deoxy-d-glucose (2DG) induces anticancer effects through glycolytic inhibition but it may raise the risk of arrhythmia. The rare monosaccharide d-allose also has anticancer properties, but its cardiac effects are unknown. We examined the effects of d-allose on adenosine triphosphate (ATP) production in neonatal rat cardiomyocytes. We showed that 25 mM d-allose selectively reduced glycolytic ATP, but had minimal impact on mitochondrial ATP, while 1 mM 2DG strongly inhibited both. Furthermore, d-allose had less impact on cell viability and was less cytotoxic than 2DG; neither compound caused apoptosis. Thus, d-allose selectively diminished glycolytic ATP production with no apparent effects on cardiomyocytes.

Possible organ-protective effects of renal denervation: insights from basic studies.

Inappropriate sympathetic nervous activation is the body's response to biological stress and is thought to be involved in the development of various lifestyle-related diseases through an elevation in blood pressure. Experimental studies have shown that surgical renal denervation decreases blood pressure in hypertensive animals. Recently, minimally invasive catheter-based renal denervation has been clinically developed, which results in a reduction in blood pressure in patients with resistant hypertension. Accumulating evidence in basic studies has shown that renal denervation exerts beneficial effects on cardiovascular disease and chronic kidney disease. Interestingly, recent studies have also indicated that renal denervation improves glucose tolerance and inflammatory changes. In this review article, we summarize the evidence from animal studies to provide comprehensive insight into the organ-protective effects of renal denervation beyond changes in blood pressure.