The role of the subfornical organ in angiotensin II–salt hypertension in the rat

Osborn, John W.; Hendel, Michael D.; Collister, John P.; Ariza-Guzman, Pilar; Fink, Gregory D.

doi:10.1113/expphysiol.2011.060491

Cited by 45 publications

(61 citation statements)

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“…In many cases, SFO lesions or interruption of SFO neurotransmission attenuates thirst responses to these stimuli (Hosutt et al 1981;Mangiapane et al 1984;Osborn et al 2012;Simpson et al 1978;Routtenberg 1973, 1978;Sunn et al 2002;Thrasher et al 1982;Thunhorst et al 1999;Tiruneh et al 2013). In the present study, DREADD-induced excitation of SFO neurons produced a dose-dependent increase in water intake of water-replete mice.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of SFO neurons increases water intake Routtenberg 1973, 1978;Smith et al 1995), plasma vasopressin levels (Ferguson and Kasting 1986), and arterial blood pressure (Gutman et al 1985). Furthermore, lesion or interruption of neurotransmission in the SFO attenuates thirst, vasopressin secretion, and/or changes in sympathetic nerve activity and blood pressure in response to multiple stimuli (Hosutt et al 1981;Mangiapane et al 1984;Osborn et al 2012;Routtenberg 1973, 1978;Sunn et al 2002;Thrasher et al 1982;Thunhorst et al 1999;Tiruneh et al 2013). In addition to water homeostasis, SFO neurons have also been implicated in sodium balance.…”

Section: Subfornical Organ (Sfo) Neurons Play a Pivotal Role In Body mentioning

confidence: 99%

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

Nation

Nicoleau

Kinsman

et al. 2016

Journal of Neurophysiology

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Nation HL, Nicoleau M, Kinsman BJ, Browning KN, Stocker SD. DREADD-induced activation of subfornical organ neurons stimulates thirst and salt appetite. J Neurophysiol 115: 3123-3129, 2016. First published March 30, 2016 doi:10.1152/jn.00149.2016.-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-HAhM3D(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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Section: Discussionmentioning

confidence: 99%

Section: Subfornical Organ (Sfo) Neurons Play a Pivotal Role In Body mentioning

confidence: 99%

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

Nation

Nicoleau

Kinsman

et al. 2016

Journal of Neurophysiology

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“…23,26 In hypertension, the SFO/organum vasculosum lamina terminalis-PVN-RVLM pathway is activated in association with AT1 receptor activation. 2,17,23,26 Other brain sites, such as the median preoptic nucleus, which receives the input from the SFO and organum vasculosum lamina terminalis, are also essential to the pathogenesis of angiotensin II-induced hypertension.…”

Section: December 2013mentioning

confidence: 99%

Potential Clinical Application of Recently Discovered Brain Mechanisms Involved in Hypertension

et al. 2013

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A ccumulating evidence indicates that central activation of the sympathetic nervous system plays an important role in hypertension. [1][2][3][4][5][6][7][8] The aim of this review is to inform clinicians about the involvement of brain mechanisms in clinical hypertension and the applicability of recent findings to clinical practice. Clinicians, particularly cardiologists and nephrologists, are now initiating clinical treatment of hypertension that targets the sympathetic nervous system using novel techniques, such as catheter-based renal denervation and carotid baroreflex activation therapy.9,10 Renal denervation reduces efferent renal sympathetic activity, thereby decreasing renal tubular sodium reabsorption, supporting renal blood flow, and inhibiting the renin-angiotensin-aldosterone system, which has a blood pressure-lowering effect. In addition, it has been proposed that inhibition of central sympathetic outflow via reduced renal afferent input to the brain leads to a long-term reduction in blood pressure.11 Carotid baroreflex activation therapy reduces blood pressure and central sympathetic outflow, and the sympathoinhibitory action lasts for a much longer period than previously thought, without rapid adaptation. 12,13 In addition, the currently used antihypertensive drugs are suggested to act on the central nervous system. 7,14 Neural Mechanisms Are Re-Emerging as a Pathogenesis and Pathophysiology of HypertensionThe brain is essential for processing and integrating various stimuli from the periphery to maintain blood pressure and fluid homeostasis. 1-3 The circumventricular organs, hypothalamus, and brain stem are major brain regions contributing to this function.2 During the past several decades, however, neural mechanisms, such as arterial baroreflex function, have been considered to be involved in short-term blood pressure regulation, but not in long-term blood pressure control (ie, hypertension).1-4 Arterial baroreceptors adapt and thus cannot provide accurate negative feedback signals to the brain to maintain normal arterial pressure. Importantly, surgical removal of the afferent projections of arterial baroreceptors (sinoaortic denervation) results in a transient increase in arterial pressure but does not lead to chronic hypertension.2 These findings suggest that the renin-angiotensin system and kidney are major contributors to the pathogenesis of hypertension. 1,3,4 Several important series of studies revealed that arterial baroreflexes have a role in long-term blood pressure regulation. First, Thrasher 15 produced chronic unloading of arterial baroreceptors in dogs, in which 1 carotid sinus and the aortic depressor nerve were cut, and the carotid sinus from the remaining innervated region was isolated from the systemic arterial pressure. Baroreceptor unloading was then induced by ligating the common carotid artery proximal to the innervated sinus, which led to an increase in arterial pressure that lasted for several weeks; although the initial increase in arterial pressure was not sustained, the l...

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“…for 2 wk) (14,15,21,28). In our experience, the model generated using this method occasionally fails to demonstrate the slow pressor effect and sustained rise in pressure that is characteristic of the model.…”

mentioning

confidence: 99%

Comparison of arterial pressure and plasma ANG II responses to three methods of subcutaneous ANG II administration

Kuroki

Fink

Osborn

2014

American Journal of Physiology-Heart and Circulatory Physiology

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Kuroki MT, Fink GD, Osborn JW. Comparison of arterial pressure and plasma ANG II responses to three methods of subcutaneous ANG II administration. Am J Physiol Heart Circ Physiol 307: H670-H679, 2014. First published July 3, 2014; doi:10.1152/ajpheart.00922.2013.-Angiotensin II (ANG II)-induced hypertension is a commonly studied model of experimental hypertension, particularly in rodents, and is often generated by subcutaneous delivery of ANG II using Alzet osmotic minipumps chronically implanted under the skin. We have observed that, in a subset of animals subjected to this protocol, mean arterial pressure (MAP) begins to decline gradually starting the second week of ANG II infusion, resulting in a blunting of the slow pressor response and reduced final MAP. We hypothesized that this variability in the slow pressor response to ANG II was mainly due to factors unique to Alzet pumps. To test this, we compared the pressure profile and changes in plasma ANG II levels during subcutaneous ANG II administration (150 ng·kg Ϫ1 ·min Ϫ1 ) using either Alzet minipumps, iPrecio implantable pumps, or a Harvard external infusion pump. At the end of 14 days of ANG II, MAP was highest in the iPrecio group (156 Ϯ 3 mmHg) followed by Harvard (140 Ϯ 3 mmHg) and Alzet (122 Ϯ 3 mmHg) groups. The rate of the slow pressor response, measured as daily increases in pressure averaged over days 2-14 of ANG II, was similar between iPrecio and Harvard groups (2.7 Ϯ 0.4 and 2.2 Ϯ 0.4 mmHg/day) but was significantly blunted in the Alzet group (0.4 Ϯ 0.4 mmHg/day) due to a gradual decline in MAP in a subset of rats. We also found differences in the temporal profile of plasma ANG II between infusion groups. We conclude that the gradual decline in MAP observed in a subset of rats during ANG II infusion using Alzet pumps is mainly due to pumpdependent factors when applied in this particular context. salt-sensitive hypertension; angiotensin II-salt hypertension; Alzet minipump; iPrecio pump; plasma angiotensin II ANG II-INDUCED HYPERTENSION is a commonly studied model of experimental hypertension, particularly in rodents. This popularity has been fueled by the prominent role that ANG II plays in cardiovascular homeostasis and various disease states such as hypertension and heart failure. Additionally, the relative ease of generating hypertension in normal animals with a defined time of onset (allowing for a within-group experimental design) without additional manipulations that are often required in other models, such as removal of a kidney and provision of salt in the drinking water, have made it an attractive model. The ANG II-induced model also involves multiple mechanisms spanning various research disciplines including autonomic neuroscience, nephrology, vascular biology, and immunology. As a consequence, the ANG II-induced model is widely used with multiple species [e.g., mice (29), rats (14, 15), dogs (17), rabbits (18) and sheep (6)], routes of administration [e.g., intravenous (27), intraperitoneal (24), subcutaneous (14, 15), and intracere...

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The role of the subfornical organ in angiotensin II–salt hypertension in the rat

Cited by 45 publications

References 44 publications

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

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

Potential Clinical Application of Recently Discovered Brain Mechanisms Involved in Hypertension

Comparison of arterial pressure and plasma ANG II responses to three methods of subcutaneous ANG II administration

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