Apelin and Vasopressin: The Yin and Yang of Water Balance

Abstract

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.

Secondary hormonal alterations in short-term severe hypothyroidism; in the focus: Apelin and copeptin

“…In addition to the elevation of copeptin levels, the altered secretion of further humoral factors may also play a role in the development of hyponatremia in SIAD. For example, the sexand age-adjusted plasma levels for apelin and copeptin are 26% and 75% higher, respectively, in SIAD patients compared to healthy subjects (1,13). The plasma apelin/copeptin ratio lies outside of the predicted range in 86% of SIAD patients.…”

“…Hyponatremia, defined as plasma sodium concentration below 135 mmol/L, is the most common electrolyte disorder in hospitalized patients ( 1 ). Various conditions have been associated with hyponatremia, including chronic heart failure, chronic kidney disease, liver cirrhosis, hypovolemia, and the syndrome of inappropriate antidiuresis (SIAD), in which antidiuretic hormone (ADH)/arginine vasopressin (AVP) secretion occurs in the absence of an osmotic or hemodynamic abnormality ( 1 , 2 ). Fluid–electrolyte imbalances, including impaired free water excretion, are common in hypothyroidism.…”

“…Apelin is particularly abundant in the hypothalamic supraoptic and paraventricular nuclei, where it colocalizes with ADH/AVP in magnocellular neurons ( 15 – 18 ), blocking the ADH/AVP secretion. Apelin increases aqueous diuresis by increasing renal blood flow and by counteracting the antidiuretic effect of ADH/AVP on the distal convoluted and collecting tubules of the kidney ( 1 , 19 ). Thus, apelin seems to play a key role in maintaining the fluid homeostasis.…”

“…In physiological conditions, ADH/AVP and apelin are released in balanced proportions from the magnocellular ADH/AVP neurons at levels appropriate for the current plasma osmolality ( 1 ). Following water deprivation, ADH/AVP is released from magnocellular vasopressinergic neurons into the bloodstream more rapidly than it is synthesized, causing the depletion of ADH/AVP in magnocellular neurons.…”

“…Hypoxia leads to the release of hypoxia-inducible factor (HIF-1) that upregulates the apelinergic signaling. However, it is not known how hypovolemia itself modulates the apelinergic system ( 1 , 31 ).…”