The angiotensin receptor subtype AT1A predominates in rat forebrain areas involved in blood pressure, body fluid homeostasis and neuroendocrine control

The organum vasculosum of the lamina terminalis (OVLT) plays a pivotal role in body fluid homeostasis and arterial blood pressure (ABP) regulation. The OVLT lacks a complete blood-brain-barrier and responds to an array of circulating factors such as NaCl and angiotensin II. Lesion of the anteroventral third ventricular region which includes the OVLT attenuates or reverses several forms of salt-sensitive hypertension. However, there is limited evidence to demonstrate that direct activation of OVLT neurons alters body fluid homeostasis or elevates ABP. To address this question, Male-Sprague-Dawley rats (300-350 g) received an injection of rAAV9-CamKII-hChR2(H134R)-EYFP (10 12 particles/mL, 200nL) into the OVLT. A fiber optic cannula (200μm) was implanted 300μm dorsal to OVLT. Approximately 2-3 week later, optogenetic activation of OVLT neurons (10ms pulse, 50% duty cycle, 30 min) produced frequency-dependent increases in water intake (1Hz: 1.0±0.5mL; 5Hz: 4.2±0.6mL; 10Hz: 8.0±1.8; 20Hz: 10.2±2.1mL, n=4, P<0.05). In separate experiments, optogenetic activation of OVLT neurons produced a frequency-dependent increase in mean ABP (1Hz: 1±1 mmHg; 5Hz: 3±1mmHg; 10Hz: 7±1mmHg; 20Hz: 13±1mmHg, n=4, P<0.05) and heart rate (1Hz: 3±6 bpm; 5Hz: 15±5bpm; 10Hz: 40±12 bpm; 20Hz: 62±14bpm, n=4, P<0.05). Pretreatment with the vasopressin antagonist Manning Compound (10ug/kg, IV) did not affect these responses. However, pretreatment with the ganglionic blocker chlorisondamine (5mg/kg, IV) abolished the pressor (20Hz: 1±1 mmHg, P<0.01) and tachycardic (20Hz: 4±7 bpm, P<0.05) responses to activation of OVLT neurons. Finally, in vivo single-unit recordings demonstrate that optogenetic activation produced frequency-dependent increases in cell discharge of OVLT neurons responsive to either intracarotid injection of hypertonic NaCl (0.3M NaCl, 50μL over 10 s, n=6) or angiotensin II (100ng over 10s, n=3). Collectively, these data provide evidence that direct activation of OVLT neurons stimulates thirst and produces a sympathetically-mediated increase in ABP.

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Neuroendocrine Control of Body Fluid Metabolism

Physiological Reviews ◽

10.1152/physrev.00017.2003 ◽

2004 ◽

Vol 84 (1) ◽

pp. 169-208 ◽

Cited By ~ 294

Author(s):

JOSÉ ANTUNES-RODRIGUES ◽

MARGARET DE CASTRO ◽

LUCILA L. K. ELIAS ◽

MARCELO M. VALENÇA ◽

SAMUEL M. McCANN

Keyword(s):

Body Fluid ◽

Defense Mechanism ◽

Third Ventricle ◽

Extracellular Fluid ◽

Volume Overload ◽

Body Fluids ◽

Potent Inducer ◽

Neuroendocrine Control ◽

Fluid Homeostasis ◽

Body Fluid Homeostasis

Antunes-Rodrigues, José, Margaret de Castro, Lucila L. K. Elias, Marcelo M. Valença, and Samuel M. McCann. Neuroendocrine Control of Body Fluid Metabolism. Physiol Rev 84: 169–208, 2004; 10.1152/physrev.00017.2003.—Mammals control the volume and osmolality of their body fluids from stimuli that arise from both the intracellular and extracellular fluid compartments. These stimuli are sensed by two kinds of receptors: osmoreceptor-Na+receptors and volume or pressure receptors. This information is conveyed to specific areas of the central nervous system responsible for an integrated response, which depends on the integrity of the anteroventral region of the third ventricle, e.g., organum vasculosum of the lamina terminalis, median preoptic nucleus, and subfornical organ. The hypothalamo-neurohypophysial system plays a fundamental role in the maintenance of body fluid homeostasis by secreting vasopressin and oxytocin in response to osmotic and nonosmotic stimuli. Since the discovery of the atrial natriuretic peptide (ANP), a large number of publications have demonstrated that this peptide provides a potent defense mechanism against volume overload in mammals, including humans. ANP is mostly localized in the heart, but ANP and its receptor are also found in hypothalamic and brain stem areas involved in bodyfluid volume and blood pressure regulation. Blood volume expansion acts not only directly on the heart, by stretch of atrial myocytes to increase the release of ANP, but also on the brain ANPergic neurons through afferent inputs from baroreceptors. Angiotensin II also plays an important role in the regulation of body fluids, being a potent inducer of thirst and, in general, antagonizes the actions of ANP. This review emphasizes the role played by brain ANP and its interaction with neurohypophysial hormones in the control of 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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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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