Countering the classical renin–angiotensin system

It is well-established that Ang-(1-7) counteracts the effects of Ang II in the periphery, while stimulating vasopressin release and mimicking the activity of Ang II in the brain, through interactions with various receptors. The rapid metabolic inactivation of Ang-(1-7) has proven to be a limitation to therapeutic administration of the peptide. To circumvent this problem, Alves et al. (Clinical Science (2021) 135(18), https://doi.org/10.1042/CS20210599) developed a new transgenic rat model that overexpresses an Ang-(1-7)-producing fusion protein. In this commentary, we discuss potential concerns with this model while also highlighting advances that can ensue from this significant technical feat.

Copeptin; utility in paediatric patients with hyponatraemia

Introduction Copeptin concentrations are a useful component of the diagnostic work-up of paediatric patients with polyuria and polydipsia but the value of measuring copeptin in patients with hyponatraemia is less clear. Case Reports We report 5 children with hyponatraemia in the context of different underlying pathologies. Copeptin concentrations were elevated in 4 cases (13.7, 14.4, 26.1, 233pmol/L; reference range 2.4 – 8.6pmol/L) suggesting that non-osmoregulated vasopressin release (syndrome of inappropriate antidiuretic diuretic hormone or SIADH) was the underlying mechanism for the low sodium levels. In one of the patients there was an underlying diagnosis of Schaaf-Yang syndrome (MAGEL 2 gene mutation) with a clinical picture suggestive of dysregulated vasopressin production with inappropriately high and then low copeptin release. In one hyponatraemic patient, low copeptin concentrations indicated that non-osmoregulated AVP release was not the cause of hyponatraemia and oliguria. Discussion Copeptin measurement did not influence management acutely but helped to clarify the mechanism leading to hyponatraemia when the result was available. Relatively high and low copeptin concentrations in association with hypo and hypernatraemia indicates dysregulated vasopressin production in Schaaf-Yang syndrome. Profound copeptin elevation may be a clue to underlying sepsis.

Prescribed Water Intake in Autosomal Dominant Polycystic Kidney Disease

In patients with autosomal dominant polycystic kidney disease (ADPKD), drinking more water could potentially reduce urine osmolality and suppress arginine vasopressin release and decrease the rate of kidney cyst growth and its associated organ dysfunction. In a 3-year trial, adults with ADPKD randomized to drink more water so as to lower urine osmolality did not have slower kidney growth than did a group who drank water as they wished.

Severe Hypernatremia in a Significantly Underweight Female Child

In this study, we present the case of a 5-year-old female who presented for evaluation of dehydration with labs that revealed significant hypernatremia concerning for diabetes insipidus (DI). Further evaluation revealed that she had underlying chronic malnutrition. Her diagnostic work up for DI produced some evidence consistent with DI while other data indicated otherwise, bringing up the possibility of partial DI. She was ultimately diagnosed with sporadic vasopressin release secondary to her chronic malnutrition. This case illustrates another effect chronic malnutrition can have on pediatric patients along with the importance of a broad differential for patients with severe hypernatremia.

Improvement of outcome prediction of hospitalized patients with COVID-19 by a dual marker strategy using high-sensitive cardiac troponin I and copeptin

Background COVID-19 has been associated with a high prevalence of myocardial injury and increased cardiovascular morbidity. Copeptin, a marker of vasopressin release, has been previously established as a risk marker in both infectious and cardiovascular disease. Purpose Investigate the prognostic impact of copeptin and high-sensitive cardiac troponin I (hs-cTnI) in COVID-19. Methods This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from June 6th to November 26th, 2020 in a tertiary care hospital. Copeptin and hs-cTnI levels on admission were collected and tested for their association with the primary composite endpoint of ICU admission or 28-day mortality. Results A total of 213 eligible patients with COVID-19 were included of whom 55 (25.8%) reached the primary endpoint. Median levels of copeptin and hs-cTnI at admission were significantly higher in patients with an adverse outcome (Copeptin 29.6 pmol/L, [IQR, 16.2–77.8] vs 17.2 pmol/L [IQR, 7.4–41.0] and hs-cTnI 22.8 ng/L [IQR, 11.5–97.5] vs 10.2 ng/L [5.5–23.1], P<0.001 respectively). ROC analysis demonstrated an optimal cut-off of 19.6 pmol/L for copeptin and 16.2 ng/L for hs-cTnI and an increase of either biomarker was significantly associated with the primary endpoint. The combination of raised hs-cTnI and copeptin yielded a superior prognostic value to individual measurement of biomarkers and was a strong prognostic marker upon multivariable logistic regression analysis (OR 4.274 [95% CI, 1.995–9.154], P<0.001). Addition of copeptin and hs-cTnI to established risk models improved C-statistics and net reclassification indices. Conclusion The combination of raised copeptin and hs-cTnI upon admission is an independent predictor of deterioration (ICU admission) or 28-day mortality in hospitalized patients with COVID-19. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Bürgermeisterfond der Stadt WienLudwig Boltzmann Cluster for Cardiovascular ResearchAssociation for the Promotion of Research on Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB) Copeptin and hs-cTnI in COVID-19 Biomarker based risk assessment

Social boldness in male green anole lizards correlates with baseline vasopressin activity

Across species, individuals within a population differ in their level of boldness in social encounters with conspecifics. This boldness phenotype is often stable across both time and social context (e.g., reproductive versus agonistic encounters). Various neural and hormonal mechanisms have been suggested as underlying these stable phenotypic differences, which are often also described as syndromes, personalities, and coping styles. Most studies examining the neuroendocrine mechanisms associated with behavioral boldness examine subjects after they have engaged in a social interaction, whereas baseline neural activity that may predispose behavioral variation is understudied. The present study tests the hypotheses that physical characteristics, steroid hormone levels, and baseline variation in Ile3-vasopressin (VP, a.k.a., Arg8-vasotocin) signaling predispose social boldness. Behavioral boldness in agonistic and reproductive contexts was extensively quantified in male green anole lizards (Anolis carolinensis), an established research organism for social behavior research that provides a crucial comparison group to investigations of birds and mammals. We found high stability of boldness across time, and between agonistic and reproductive contexts. Next, immunofluorescence was used to colocalize VP neurons with phosphorylated ribosomal protein S6 (pS6), a proxy marker of neural activity. VP-pS6 colocalization within the paraventricular and supraoptic nuclei of the hypothalamus was inversely correlated with aggression boldness, but not reproductive behavior boldness. Our findings suggest that baseline vasopressin release, rather than solely context-dependent release, plays a role in predisposing individuals toward stable levels of aggressive boldness toward conspecifics by inhibiting behavioral output in these contexts.

N-Methyl-D-aspartate Glutamate Receptor Modulates Cardiovascular and Neuroendocrine Responses Evoked by Hemorrhagic Shock in Rats

Here, we report the participation of N-methyl-D-aspartate (NMDA) glutamate receptor in the mediation of cardiovascular and circulating vasopressin responses evoked by a hemorrhagic stimulus. In addition, once NMDA receptor activation is a prominent mechanism involved in nitric oxide (NO) synthesis in the brain, we investigated whether control of hemorrhagic shock by NMDA glutamate receptor was followed by changes in NO synthesis in brain supramedullary structures involved in cardiovascular and neuroendocrine control. Thus, we observed that intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK801, 0.3 mg/kg) delayed and reduced the magnitude of hemorrhage-induced hypotension. Besides, hemorrhage induced a tachycardia response in the posthemorrhage period (i.e., recovery period) in control animals, and systemic treatment with MK801 caused a bradycardia response during hemorrhagic shock. Hemorrhagic stimulus increased plasma vasopressin levels during the recovery period and NMDA receptor antagonism increased concentration of this hormone during both the hemorrhage and postbleeding periods in relation to control animals. Moreover, hemorrhagic shock caused a decrease in NOx levels in the paraventricular nucleus of the hypothalamus (PVN), amygdala, bed nucleus of the stria terminalis (BNST), and ventral periaqueductal gray matter (vPAG). Nevertheless, treatment with MK801 did not affect these effects. Taken together, these results indicate that the NMDA glutamate receptor is involved in the hemorrhagic shock by inhibiting circulating vasopressin release. Our data also suggest a role of the NMDA receptor in tachycardia, but not in the decreased NO synthesis in the brain evoked by hemorrhage.

Dexmedetomidine Related Polyuria and Hypernatremia in Intensive Care Unit.

Dexmedetomidine is commonly used sedative nowadays. It’s being used as an anesthetic for surgical procedures and frequently being used in ICU Settings for sedation, and analgesia. Dexmedetomidine is a highly selective, alpha-2 agonist that also blocks arginine-vasopressin release. Dexmedetomidine is suspected to cause diabetes insipidus leading to polyuria and hypernatremia. We report a case of Diabetes Insipidus associated with use of dexmedetomidine.