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.

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AT1a influences GABAA-mediated inhibition through regulation of KCC2 expression

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00105.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. R972-R982 ◽

Cited By ~ 2

Author(s):

George E. Farmer ◽

Kirthikaa Balapattabi ◽

Martha E. Bachelor ◽

Joel T. Little ◽

J. Thomas Cunningham

Keyword(s):

Protein Expression ◽

Body Fluid ◽

Neuronal Excitability ◽

Receptor Activation ◽

Cardiovascular Control ◽

Ang Ii ◽

Sprague Dawley ◽

Fluid Homeostasis ◽

Body Fluid Homeostasis

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.

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DREADD-induced activation of subfornical organ neurons stimulates thirst and salt appetite

Journal of Neurophysiology ◽

10.1152/jn.00149.2016 ◽

2016 ◽

Vol 115 (6) ◽

pp. 3123-3129 ◽

Cited By ~ 33

Author(s):

Haley L. Nation ◽

Marvin Nicoleau ◽

Brian J. Kinsman ◽

Kirsteen N. Browning ◽

Sean D. Stocker

Keyword(s):

Water Intake ◽

Body Fluid ◽

Subfornical Organ ◽

Designer Drugs ◽

Salt Appetite ◽

Fluid Homeostasis ◽

Body Fluid Homeostasis ◽

Acute Injection

The subfornical organ (SFO) plays a pivotal role in body fluid homeostasis through its ability to integrate neurohumoral signals and subsequently alter behavior, neuroendocrine function, and autonomic outflow. The purpose of the present study was to evaluate whether selective activation of SFO neurons using virally mediated expression of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) stimulated thirst and salt appetite. Male C57BL/6 mice (12–15 wk) received an injection of rAAV2-CaMKII-HA-hM3D(Gq)-IRES-mCitrine targeted at the SFO. Two weeks later, acute injection of clozapine N-oxide (CNO) produced dose-dependent increases in water intake of mice with DREADD expression in the SFO. CNO also stimulated the ingestion of 0.3 M NaCl. Acute injection of CNO significantly increased the number of Fos-positive nuclei in the SFO of mice with robust DREADD expression. Furthermore, in vivo single-unit recordings demonstrate that CNO significantly increases the discharge frequency of both ANG II- and NaCl-responsive neurons. In vitro current-clamp recordings confirm that bath application of CNO produces a significant membrane depolarization and increase in action potential frequency. In a final set of experiments, chronic administration of CNO approximately doubled 24-h water intake without an effect on salt appetite. These findings demonstrate that DREADD-induced activation of SFO neurons stimulates thirst and that DREADDs are a useful tool to acutely or chronically manipulate neuronal circuits influencing body fluid homeostasis.

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Brain-Targeted (Pro) Renin Receptor Knockdown Modulates Body Fluid Homeostasis

Journal of Hypertension Open Access ◽

10.4172/2167-1095.1000160 ◽

2013 ◽

Vol 03 (04) ◽

Cited By ~ 1

Author(s):

Wencheng Li Dale Seth

Keyword(s):

Body Fluid ◽

Fluid Homeostasis ◽

Body Fluid Homeostasis

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Perioperative inﬂuences on body ﬂuid homeostasis

Perioperative Practice ◽

10.4324/9780203994283-10 ◽

2005 ◽

pp. 81-114

Keyword(s):

Body Fluid ◽

Fluid Homeostasis ◽

Body Fluid Homeostasis

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Physiological regulation of the renal vasopressin receptor-effector pathway in dogs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1990.258.3.r763 ◽

1990 ◽

Vol 258 (3) ◽

pp. R763-R769

Author(s):

L. B. Kinter ◽

N. Caldwell ◽

S. Caltabiano ◽

C. Winslow ◽

D. P. Brooks ◽

...

Keyword(s):

Volume Expansion ◽

Body Fluid ◽

Physiological State ◽

Extracellular Volume ◽

Conscious Dogs ◽

Physiological Regulation ◽

Fluid Homeostasis ◽

Effector Pathway ◽

Body Fluid Homeostasis ◽

V2 Receptor

Physiological regulation of receptor-effector pathways is recognized as a significant factor determining target organ selectivity and sensitivity in several hormonal systems. Whether or not physiological regulation of the renal vasopressin (V2) receptor-effector pathway participates in the control of body fluid homeostasis is unknown. We evaluated four states likely to be associated with altered sensitivities of the renal V2 receptor-effector pathway as follows: dehydration (18-h hydropenia), volume expansion, exogenous arginine vasopressin (AVP) infusion (10 ng/kg + 0.25 ng.kg-1.h-1), and cyclooxygenase blockade (indomethacin, 2 mg/kg + 2 mg.kg-1.h-1) for effects on the antidiuretic efficacies and potencies of putative V2-receptor antagonists in conscious dogs. The antidiuretic efficacies of desGly9[Pmp1-D-Tyr(Et)2Val4]AVP [Smith Kline & French (SK&F) 101926; 0.01-1,000 micrograms/kg] ranged from that of a full agonist to that of an antagonist, depending on the physiological state studied. The vasopressin antagonist potency of SK&F 101926 was increased 150-fold in association with extracellular volume expansion and decreased by blockade of renal cyclooxygenase activity. This spectrum of activities is that anticipated for a partial agonist under conditions where receptor number and/or sensitivity of receptor-effector coupling is increased or decreased, respectively. Thus volume expansion and increased circulating vasopressin concentration are associated with effective decreases, whereas hydropenia and cyclooxygenase blockade are associated with effective increases in sensitivity of the renal V2 receptor-effector pathway in the dog kidney. We conclude that the V2 receptor-effector pathway is a site of integration of physiological mechanisms participating in the control of body fluid homeostasis in conscious dogs.

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Effects of kassinin, a tachykinin of the skin of the African frog Kassina senegalensis, on body fluid homeostasis in rats

Pharmacological Research Communications ◽

10.1016/s0031-6989(88)80843-9 ◽

1988 ◽

Vol 20 ◽

pp. 67-70

Author(s):

Perfumi M. ◽

do Caro G. ◽

Panocka I. ◽

Polidori C. ◽

Massi M.

Keyword(s):

Body Fluid ◽

Fluid Homeostasis ◽

Body Fluid Homeostasis

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Stanniocalcin-1 in the subfornical organ inhibits the dipsogenic response to angiotensin II

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00057.2012 ◽

2012 ◽

Vol 303 (9) ◽

pp. R921-R928 ◽

Cited By ~ 4

Author(s):

Jason M. Moreau ◽

Waseem Iqbal ◽

Jeffrey K. Turner ◽

Graham F. Wagner ◽

John Ciriello

Keyword(s):

Western Blot ◽

Water Intake ◽

Body Fluid ◽

Physiological Role ◽

Subfornical Organ ◽

Ang Ii ◽

Sprague Dawley ◽

Glycoprotein Hormone ◽

Fluid Homeostasis ◽

Body Fluid Homeostasis

Recently, receptors for the calcium-regulating glycoprotein hormone stanniocalcin-1 (STC-1) have been found within subfornical organ (SFO), a central structure involved in the regulation of electrolyte and body fluid homeostasis. However, whether SFO neurons produce STC-1 and how STC-1 may function in fluid homeostasis are not known. Two series of experiments were done in Sprague-Dawley rats to investigate whether STC-1 is expressed within SFO and whether it exerts an effect on water intake. In the first series, experiments were done to determine whether STC-1 was expressed within cells in SFO using immunohistochemistry, and whether protein and gene expression for STC-1 existed in SFO using Western blot and quantitative RT-PCR, respectively. Cells containing STC-1 immunoreactivity were found throughout the rostrocaudal extent of SFO. STC-1 protein expression within SFO was confirmed with Western blot, and SFO was also found to express STC-1 mRNA. In the second series, microinjections (200 nl) of STC-1, ANG II, a combination of the two or the vehicle were made into SFO in conscious, unrestrained rats. Water intake was measured at 0700 for a 1-h period after each injection in animals. Microinjections of STC-1 (17.6 or 176 nM) alone had no effect on water intake compared with controls. However, STC-1 not only attenuated the drinking responses to ANG II for about 30 min, but also decreased the total water intake over the 1-h period. These data suggest that STC-1 within the SFO may act in a paracrine/autocrine manner to modulate the neuronal responses to blood-borne ANG II. These findings also provide the first direct evidence of a physiological role for STC-1 in central regulation of body fluid homeostasis.

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