Hypomagnesaemia is a common feature of renal Na+ wasting disorders such as Gitelman and EAST/SeSAME syndrome. These genetic defects specifically affect Na+ reabsorption in the distal convoluted tubule, where Mg2+ reabsorption is tightly regulated. Apical uptake via TRPM6 Mg2+ channels and basolateral Mg2+ extrusion via a putative Na+‐Mg2+ exchanger determines Mg2+ reabsorption in the distal convoluted

The involvement of Septate Junctions (SJs) in critical cellular functions that extend beyond their role as diffusion barriers in the epithelia and the nervous system has made the fruit‐fly an ideal model for the study of human diseases associated with impaired Tight Junction (TJ) function. In this study, we summarized current knowledge of the Drosophila melanogaster SJ‐related proteins, focusing on

The tools that have been used to assess the function of the vagus nerve lack specificity. This could explain discrepancies about the role of vagal gut‐brain signaling in long‐term control of energy balance. Here we use a validated approach to selectively ablate sensory vagal neurons that innervate the gut to determine the role of vagal gut‐brain signaling in the control of food intake, energy expenditure

We investigated potential neuron types that code sugar information and how sodium‐glucose cotransporters (SGLTs) and T1Rs are involved.

Exercise is a key component of a healthy lifestyle as it helps maintain a healthy body weight and reduces the risk of various morbidities and co‐morbidities. Exercise is an acute physiological stress that initiates a multitude of processes that attempt to restore physiological homeostasis and promote adaptation. A component of the stress response to exercise is the rapid release of hormones from the

Finally, I (PBP) discovered the right book for me. After starting a few other ones, putting them down, forcing myself to read on, taking another break, I abandoned the book pile with a bad conscious. After weeks of search, this is my page‐turner, keeping me up at night. It seems the book is rather special, being the story of a journalist's parents who meet in Norway during the Nazi occupation.1 What

Hypertension is the primary cause of cardiovascular mortality. Despite multiple existing treatments, only half of those with the disease achieve adequate control. Therefore, understanding the mechanisms causing hypertension is essential for the development of novel therapies. Many studies demonstrate that immune cell infiltration of the vessel wall, kidney and central nervous system, as well as their

Several Na+‐dependent phosphate cotransporters namely NaPi‐IIb/SLC34A3, Pit‐1/SLC20A1 and Pit‐2/SLC20A2, are expressed at the apical membrane of enterocytes but their contribution to active absorption of phosphate is unclear. The aim of this study was to compare their pattern of mRNA expression along the small and large intestine and to analyse the effect of intestinal depletion of Pit‐2 on phosphate

It has long been known that cardiac myocytes release ATP, and that the release of ATP is increased in response to hypoxia and ischaemia. The mechanisms underlying that release and its regulation, however, remain unclear. In this issue of Acta Physiologica , Wang and colleagues from the Ballard lab present intriguing new evidence of a role for the cystic fibrosis transmembrane conductance regulator

In this issue of Acta Physiologia , Pallubinsky et al .1 report that repeated moderate heat exposure has beneficial effects on blood glucose levels and insulin sensitivity in overweight, but otherwise healthy subjects, suggesting ambient temperature driven responses as efficient approach to the treatment of early diabetes symptoms.

Tian and colleagues highlight the importance of right and left ventricular interdependence in their article in this issue of Acta Physiologica. The role of the right ventricle is often underestimated in health and disease. In comparison with the left ventricle, the right ventricle is triangular shaped whereas the left ventricle is conical. Right ventricular function has been shown to be an important

Currently, the Covid‐19 pandemic forces almost every country to take drastic measures to stop the spread of the virus. These include the avoidance of close contact with other humans, staying at home whenever possible and the closure of gyms or sport clubs. Now that people are more or less bound to their home, it is even more important to stay physically active. The occasional walks between sofa and

The aim of the study was to investigate the role of cytochrome P450 (CYP) epoxygenase‐derived epoxyeicosatrienoic acids (EETs) in sustained hypoxic pulmonary vasoconstriction (HPV).

The new coronavirus SARS‐COV‐2 is currently impacting life around the globe.1 The rapid spread of this viral disease might be highly challenging for health care systems. This was seen in Northern Italy and in New York City for example.2 Governments reacted with different measures such as shutdown of all schools, universities and up to a general curfew. All of those measures have a huge impact on the

SLC26A3 (DRA) mediates the absorption of luminal Cl− in exchange for HCO3− in the distal intestine. Its expression is lost in congenital chloride diarrhoea (CLD) and strongly decreased in the presence of intestinal inflammation. To characterize the consequences of a loss of Slc26a3 beyond disturbed electrolyte transport, colonic mucus synthesis, surface accumulation and composition, pH microclimate

Obesity has become a pandemic that affects all populations of all ages living in countries of all income levels.1 Attributed to sedentary lifestyle and energy dense diet, obesity is a risk factor for cardiovascular disease, insulin resistance, type 2 diabetes and even some types of cancer.2 These comorbidities also affect the immune system adversely and can exacerbate infectious diseases as observed

Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in the heart, but its function there is unclear. CFTR regulates an ATP release pore in many tissues, but the identity and regulatory mechanism of the pore are unknown. We investigated the role of CFTR in ATP release from primary cardiomyocytes and ventricular wall in vivo.

FMS‐like receptor tyrosine kinase 3 (Flt3) has been reported to be increased in cardiomyocytes responding to ischaemic stress. This study was to determine whether Flt3 activation could ameliorate pressure overload‐induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action.

The renin angiotensin system (RAS) plays an important role in the pathogenesis of variety of diseases. Targeting the formation and action of angiotensin II (Ang II), the main RAS peptide, has been the key therapeutic target for last three decades. ACE‐related carboxypeptidase (ACE2), a monocarboxypeptidase that had been discovered 20 years ago, is one of the catalytically most potent enzymes known

MRP2 is an intestinal ABC transporter that prevents the absorption of dietary xenobiotics. The aims of this work were: (1) to evaluate whether a short‐term regulation of intestinal MRP2 barrier function takes place in vivo after luminal incorporation of nutrients and (2) to explore the underlying mechanism.

Low skeletal muscle mass is highly prevalent in older cancer patients and affects 5% to 89% depending on the type and stage of cancer. Low skeletal muscle mass is associated with poor clinical outcomes such as postoperative complications, chemotherapy toxicity and mortality in older cancer patients. Little is known about the mediating pathophysiological mechanisms. In this review we summarize proposed

Sodium retention is the hallmark of nephrotic syndrome (NS) and mediated by the proteolytic activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases. Plasmin is highly abundant in nephrotic urine and has been proposed to be the principal serine protease responsible for ENaC activation in NS. However, a proof of the essential role of plasmin in experimental NS is lacking

Surprises are not always welcome. We have studied total body water, quantified the volume and determined the extracellular space, interstitial, and plasma volumes. Nonetheless, estimating these parameters clinically (at the bedside) is frustratingly imprecise. The author ruminates over 50 years’ clinical experience in intensive care units and grapples with the literature. The critical fluid‐replacement

Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and Ulcerative colitis (UC) have a complex and multifactorial pathogenesis which is incompletely understood. A typical feature closely associated with clinical symptoms is impaired intestinal epithelial barrier function. Mounting evidence suggests that desmosomes, which together with tight junctions (TJ) and adherens junctions (AJ) form

In the current issue of Acta Physiologica, Lawrence et al1 provide a rigorous investigation into the effects of mechanical massage therapy on skeletal muscle during normal weight bearing (WB) and unloading conditions. One week of hindlimb suspension (HS) in rats was used to determine if massage is an effective therapy to blunt disuse associated muscle loss. Massage therapy increased the muscle protein

AIM Resistance exercise increases muscle mass over time. However, the early signalling events leading to muscle growth are not yet well-defined. Here, we aim to identify new signalling pathways important for muscle remodelling after exercise METHODS: We performed a phosphoproteomics screen after a single bout of exercise in mice. As an exercise model we used unilateral electrical stimulation in vivo

AIM Herein we propose creating a bilayer tubular kidney in-vitro model. It is hypothesized that membranes composed of decellularized porcine kidney extracellular matrix are valid substitutes of the tubular basement membrane by mimicking the physiological relevance of the in vivo environment and disease phenotypes. METHODS Extracellular matrix was obtained from decellularized porcine kidneys. After

We wish to respond to the opinions stated in the accompanying letter regarding our manuscript, “Deregulated hypoxic response in myeloid cells: A model for high‐altitude pulmonary oedema (HAPE)” by Gojkovic et al. In essence, Swenson and Bärtsch state that the deletion of VHL in myeloid cells cannot be a model for human HAPE because, in their view, human HAPE is in no way an inflammatory syndrome, whereas

AIM The voltage-gated sodium channel NaV 1.5, encoded by SCN5A, is essential for cardiac excitability and ensures proper electrical conduction. Early embryonic death has been observed in several murine models carrying homozygous Scn5a mutations. We investigated when sodium current (INa ) becomes functionally relevant in the murine embryonic heart and how Scn5a/NaV 1.5 dysfunction impacts on cardiac

AIM How can we convert biomarkers into reliable, validated laboratory tests? Glomerular filtration rate (GFR) estimators exist for more than a century. The first utilitarian biomarkers were endogenously produced urea and creatinine. Clinicians then developed simple tests to determine whether or not renal tubular function was maintained. Are there faster and better tests that reflect decreased renal

Despite our growing understanding of the patho-physiological mechanisms underlying the different subtypes of long-QT syndrome (LQTS), current treatment approaches in this disease target the pro-arrhythmic sympathetic trigger (by beta-blockade or left-cardiac sympathetic denervation) or terminate ventricular arrhythmias once they occur (by implantable cardioverter defibrillators).

Reactive oxygen species (ROS) are produced by the aerobic metabolism. The imbalance between production of ROS and antioxidant defence in any cell compartment is associated with cell damage and may play an important role in the pathogenesis of renal disease. NADPH oxidase (NOX) family is the major ROS source in the vasculature and modulates renal perfusion. Upregulation of Ang II and adenosine activates

AIM Adipose-derived stem cells (ASCs) therapies are emerging as a promising approach to therapeutic angiogenesis. Therapeutic persistence and reduced primitive stem cell function following cell delivery remains a critical hurdle for the clinical translation of stem cells in current approaches. METHODS Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal

We analysed the importance of systemic and peripheral arteriovenous O2 difference (a- v - O2 and a-vf O2 difference, respectively) and O2 extraction fraction for maximal oxygen uptake ( V ˙ O2max ). Fick law of diffusion and the Piiper and Scheid model were applied to investigate whether diffusion vs perfusion limitations vary with V ˙ O2max . Articles (n=17) publishing individual data (n=154) on V

Mitochondrial affinity for oxygen was recently demonstrated to increase after sprint training and turned out to be closely associated with training‐related improvement in pulmonary peak oxygen uptake (VO2peak) during both arm cranking and leg cycling.1 Although logically the final step of the oxygen cascade should be modulated by mitochondrial oxygen affinity with notable impact on VO2peak, experimental

Heat exposure has been indicated to positively affect glucose metabolism. An involvement of heat shock protein 72 (HSP72) in the enhancement of insulin sensitivity upon heat exposure has been previously suggested. Here, we performed an intervention study exploring the effect of passive heat acclimation (PHA) on glucose metabolism and intracellular (a) HSP72 concentrations in overweight humans.

An intriguing local epithelial enzyme contribution to renal medullary urea accumulation and ischemic tolerance was uncovered in a study by Ansermet et al1 published in the present issue of Acta Physiologica . It was shown in vivo in mice with tubular epithelial‐specific deletion of the enzyme L‐arginase type 2 (ARG2) that ARG2 contributed to medullary urea accumulation, through its hydrolysis of L‐arginine

We read and studied with great anticipation the article by Gojkovic et al. (1) and the accompanying editorial by Nikinmaa (2) in the present issue reporting on a new mouse model of high altitude pulmonary edema (HAPE). For investigators in the field, particularly those of us researching and treating HAPE in humans, an animal model for HAPE has been a quest for the holy grail for 60 years (3). A good

AIM Pulmonary arterial hypertension (PAH) results in right ventricular (RV) dysfunction owing, in part, to RV ischemia. The relative contribution of RV microvascular rarefaction vs reduced right coronary artery perfusion pressure (RCA-PP) to RV ischemia remains unknown. We hypothesize that increasing RCA-PP improves RV function in PAH by increasing RV systolic perfusion. METHODS Supra-coronary aortic

For a long time, the vascular tone was considered to be regulated exclusively by tonic innervation of vasoconstrictor adrenergic nerves. However, accumulating experimental evidence has revealed the existence of nerves mediating vasodilatation, including perivascular nitrergic nerves (PNN), in a wide variety of mammalian species. Functioning of nitrergic vasodilator nerves is evidenced in several territories

Metabolomics is now, after genomics, transcriptomics and proteomics, one of the ‐omics that is beginning to expand into clinical diagnostics. This progress has been achieved by the recent development of high‐throughput screening methods. We are all familiar with metabolites like sugars, amino acids, lipids or nucleotides. But there are many more of these small molecules. Metabolites include all intermediates

In the current issue of Acta Physiologica, Nielsen and co‐workers publish a paper entitled "Regulation of integrin alpha6 by lactogenic hormones in rat pancreatic beta‐cells: Implications for the physiological adaptation to pregnancy" in which the authors describe a novel pathway for increased beta‐cell replication in response to lactogenic hormones like prolactin and growth hormone, both key players

In the United States in 2019, every 40 seconds someone suffers a myocardial infarction and every 37 seconds someone dies of cardiovascular disease (CVD)1 . The annual total cost of CVD in the United States was estimated at $351.2 billion1 . There are many risk factors that can explain high CV mortality in an era of modern therapeutic approaches, but a significant proportion of this mortality might

AIM Serotonin is crucial for proper foetal development, and the placenta has been described as a 'donor' of serotonin for the embryo/foetus. However, in later stages of gestation the foetus produces its own serotonin from maternally-derived tryptophan and placental supply is no longer needed. We propose a novel model of serotonin homeostasis in the term placenta with special focus on the protective

We aimed to assess the ability of natural and modified polyunsaturated fatty acids (PUFAs) to shorten QT interval in ex‐vivo and in‐vivo guinea pig hearts.

Surging interest on how growth hormone (GH) affects the central nervous system (CNS) is apparent over the latest decades. Various clinics and basic science laboratories suggest important function of GH for many behavioural aspects.1-3 New light is shed on GHs influence on cognitive functions by Martin‐Rodriguez and co‐workers in the present volume of Acta Physiologica by implementing ground‐breaking

When low‐altitude people rapidly ascend to altitudes above 2500 m, they run a risk of developing high‐altitude pulmonary edema (HAPE).1 The first scientific report in an English‐written journal was published in 1960,2 and still in 1975 the article by Kleiner and Nelson in JAMA had a title: High‐altitude pulmonary edema: A rare disease?3 However, as tourism at high altitudes has become common and as

The new coronavirus, classified as severe acute respiratory syndrome (SARS)‐CoV‐2 that emerged in Hubei province in China, causes a new coronavirus disease, which was termed COVID‐19 by WHO on 11 February 2020. COVID‐19 claimed more than 65 000 lives around the world by 5th of April 2020. It is not the first coronavirus, which infects humans; the pathogenic viruses that cause human diseases (human

We are living in times where a viral disease has brought normal life in much of the world to a halt. Named after its causative agent, coronavirus disease 2019 (COVID‐19) is caused by a novel coronavirus recently renamed as severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).1 Coronavirus disease 2019 manifests as dry cough, frequent fevers and in severe cases pneumonia. Older patients and

Sir George W. Pickering was an astute, opinionated observer and highly gifted cardiovascular investigator. He considered the rich history of cardiovascular research, settled on the term “essential hypertension” (although he did not like it much) and left us with two challenges and then outlined three areas of investigation, namely animal models, human translational studies and genetics to pursue. These

The mitochondrial GTPase, OPA1 (Optic Atrophy 1) plays a major role in mitochondrial structure and function, regulating both the fusion of membranes and cristae ultrastructure 1. OPA1 is associated with a wide range of pathologies in which mitochondrial dysfunction occurs, including neurodegenerative and cardiac diseases, as well as primary mitochondrial diseases such as dominant optic atrophy, Behr

Diabetes mellitus had a global prevalence of 8.5 % in 2014; in other words 422 million people were affected. This chronic metabolic disease is not only common in wealthy countries, but it is also rising in those of middle and low income. The World Health Organization (WHO) declared diabetes as one of the leading causes of death in the world.

To study brain‐sparing physiological responses in a rodent model of birth asphyxia which reproduces the asphyxia‐defining systemic hypoxia and hypercapnia.

Within the current paradigm of the myonuclear domain theory, it is postulated that a linear relationship exists between muscle fibre size and myonuclear content. The myonuclear domain is kept (relatively) constant by adding additional nuclei (supplied by muscle satellite cells) during muscle fibre hypertrophy and nuclear loss (by apoptosis) during muscle fibre atrophy. However, data from recent animal

It is debated whether the inhibition of glucagon secretion by glucose results from direct effects of glucose on the α‐cell (intrinsic regulation) or by paracrine effects exerted by beta‐ or delta‐cell products.

The body responds to exercise training by profound adaptations throughout the cardiorespiratory and muscular systems, which may result in improvements in maximal oxygen consumption (VO2peak) and mitochondrial capacity. By convenience, mitochondrial respiration is often measured at supra‐physiological oxygen levels, an approach that ignores any potential regulatory role of mitochondrial affinity for

Since 1812 children recite1: Mirror, mirror, on the wall, Who in this land is fairest of all? It answered: You, my queen, are fair; it is true. But Snow‐White is a thousand times fairer than you. The queen took fright and turned yellow and green with envy… Would beauty come with impact factors, the queen's vain enquiry would probably have remained unanswered. Nonetheless, when it comes to physiology

AIM High altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that can occur during rapid ascent to a high-altitude environment. Classically, HAPE has been described as a condition resulting from a combination of pulmonary vasoconstriction and hypertension. Inflammation has been described as important in HAPE, although as a side effect of pulmonary edema rather than as a causative factor

Interventions that decrease atrophy during disuse are desperately needed to maintain muscle mass. We recently found that massage as a mechanotherapy can improve muscle regrowth following disuse atrophy. Therefore, we aimed to determine if massage has similar anabolic effects when applied during normal weight bearing conditions (WB) or during atrophy induced by hindlimb suspension (HS) in adult rats

The voltage-gated sodium (NaV ) channel is required for cardiomyocyte function. In heart, its major, pore-forming, α-subunit is NaV 1.5, encoded by SCN5A, which maps to chromosome 3p21. The NaV channel plays a key role in myocardial excitability, since it is responsible for generating the rising phase of the cardiac action potential. NaV 1.5 often shows alterations in inherited channelopathies causing