Apelin and Vasopressin: The Yin and Yang of Water Balance

Apelin, a (neuro)vasoactive peptide, plays a prominent role in controlling body fluid homeostasis and cardiovascular functions. Experimental data performed in rodents have shown that apelin has an aquaretic effect via its central and renal actions. In the brain, apelin inhibits the phasic electrical activity of vasopressinergic neurons and the release of vasopressin from the posterior pituitary into the bloodstream and in the kidney, apelin regulates renal microcirculation and counteracts in the collecting duct, the antidiuretic effect of vasopressin occurring via the vasopressin receptor type 2. In humans and rodents, if plasma osmolality is increased by hypertonic saline infusion/water deprivation or decreased by water loading, plasma vasopressin and apelin are conversely regulated to maintain body fluid homeostasis. In patients with the syndrome of inappropriate antidiuresis, in which vasopressin hypersecretion leads to hyponatremia, the balance between apelin and vasopressin is significantly altered. In order to re-establish the correct balance, a metabolically stable apelin-17 analog, LIT01-196, was developed, to overcome the problem of the very short half-life (in the minute range) of apelin in vivo. In a rat experimental model of vasopressin-induced hyponatremia, subcutaneously (s.c.) administered LIT01-196 blocks the antidiuretic effect of vasopressin and the vasopressin-induced increase in urinary osmolality, and induces a progressive improvement in hyponatremia, suggesting that apelin receptor activation constitutes an original approach for hyponatremia treatment.

Diversification of mineralocorticoid receptor genes in a subterranean rodent, the naked mole-rat

Naked mole-rats (Heterocephalus glaber) inhabit subterranean burrows in savannas and are thus unable to access free water. To identify their mechanism of osmoregulation in xeric environments, we molecularly cloned and analyzed the mineralocorticoid receptor (MR) gene, required for hormone-dependent regulation of genes contributing to body fluid homeostasis. Most vertebrates harbor a single MR homolog. In contrast, we discovered that MR is duplicated in naked mole-rats. The amino acid sequence of naked mole-rat MR1 is 90% identical to its mouse ortholog, and MR1 is abundantly expressed in the kidney and the nervous system. MR2 encodes a truncated protein lacking DNA- and ligand-binding domains of MR1 and is expressed in diverse tissues. Although MR2 did not directly transactivate gene expression, it increased corticosteroid-dependent transcriptional activity of MR1. Our results suggest that MR2 might function as a novel regulator of MR1 activity to fine-tune MR signaling in naked mole-rats.

Urinary system

The ‘Urinary system’ chapter opens with a description of the urinary tract morphology (kidney, ureters, bladder) and its histology. Renal function is considered, including glomerular filtration, the role and regulation of the renal tubules in producing dilute and concentrated urines, and the mechanisms of action of diuretic drugs. The function of the kidney in body fluid homeostasis (extracellular fluid volume and osmolarity, pH) is then discussed, and the regulation of kidney function explored, including bladder control and urinary continence. Finally, renal failure and obstructive uropathy are discussed as examples of renal pathology.

Fluid Intake Monitoring System Using a Wearable Inertial Sensor for Fluid Intake Management

Fluid intake is important for people to maintain body fluid homeostasis. Inadequate fluid intake leads to negative health consequences, such as headache, dizziness and urolithiasis. However, people in busy lifestyles usually forget to drink sufficient water and neglect the importance of fluid intake. Fluid intake management is important to assist people in adopting individual drinking behaviors. This work aims to propose a fluid intake monitoring system with a wearable inertial sensor using a hierarchical approach to detect drinking activities, recognize sip gestures and estimate fluid intake amount. Additionally, container-dependent amount estimation models are developed due to the influence of containers on fluid intake amount. The proposed fluid intake monitoring system could achieve 94.42% accuracy, 90.17% sensitivity, and 40.11% mean absolute percentage error (MAPE) for drinking detection, gesture spotting and amount estimation, respectively. Particularly, MAPE of amount estimation is improved approximately 10% compared to the typical approaches. The results have demonstrated the feasibility and the effectiveness of the proposed fluid intake monitoring system.

AT1a influences GABAA-mediated inhibition through regulation of KCC2 expression

The median preoptic nucleus (MnPO) is an integrative site involved in body fluid homeostasis, cardiovascular control, thermoregulation, and sleep homeostasis. Angiotensin II (ANG II), a neuropeptide shown to have excitatory effects on MnPO neurons, is of particular interest with regard to its role in body fluid homeostasis and cardiovascular control. The present study investigated the role of angiotensin type 1a (AT1a) receptor activation on neuronal excitability in the MnPO. Male Sprague-Dawley rats were infused with an adeno-associated virus with an shRNA against the AT1a receptor or a scrambled control. In vitro loose-patch voltage-clamp recordings of spontaneous action potential activity were made from labeled MnPO neurons in response to brief focal application of ANG II or the GABAA receptor agonist muscimol. Additionally, tissue punches from MnPO were taken to asses mRNA and protein expression. AT1a receptor knockdown neurons were insensitive to ANG II and showed a marked reduction in GABAA-mediated inhibition. The reduction in GABAA-mediated inhibition was not associated with reductions in mRNA or protein expression of GABAA β-subunits. Knockdown of the AT1a receptor was associated with a reduction in the potassium-chloride cotransporter KCC2 mRNA as well as a reduction in pS940 KCC2 protein. The impaired GABAA-mediated inhibition in AT1a knockdown neurons was recovered by bath application of phospholipase C and protein kinase C activators. The following study indicates that AT1a receptor activation mediates the excitability of MnPO neurons, in part, through the regulation of KCC2. The regulation of KCC2 influences the intracellular [Cl−] and the subsequent efficacy of GABAA-mediated currents.