Angiotensinergic Signaling in the Brain Mediates Metabolic Effects of Deoxycorticosterone (DOCA)-Salt in C57 Mice

Grobe, Justin L; Buehrer, Beth A.; Hilzendeger, Aline M; Liu, Xuebo; Davis, Deborah R.; Xu, Di; Sigmund, Curt D.

doi:10.1161/hypertensionaha.110.165829

Cited by 94 publications

(125 citation statements)

References 30 publications

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“…More recently, the importance of AT 1A R in the SFO has been examined by genetic manipulation in mice carrying a conditional allele of the AT 1A R (AT 1A R Flox ) gene. Intracerebroventricular injection of an adenovirus encoding Cre-recombinase (AdCRE) (127,128) in AT 1A R Flox mice results in an SFO-specific decrease in the expression of AT 1A R mRNA, which attenuated the water and saline intake and blood pressure response to deoxycorticosterone acetate (DOCA) salt (44). Coupled with the discussion above, these studies highlight the importance of both ANG II production and action in the SFO in regulating blood pressure and fluid homeostasis.…”

Section: Localization Of Ras Components Required For Ang II Action: Fmentioning

confidence: 79%

“…Second, DOCA-salt and aldosterone elevates brain RAS activity within endogenous areas, resulting in increased blood pressure and fluid intake through central activation of AT 1 R (44,47,60,104,148). DOCA-salt increases c-Fos expression within the OVLT, BNST, MnPO, PVN, SON, amygdala, and preoptic area in rodents (85,140).…”

Section: Stimulators Of the Brain Ras And Physiological Effects Of Sfmentioning

confidence: 99%

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Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Coble¹,

Grobe

Johnson³

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Coble JP, Grobe JL, Johnson AK, Sigmund CD. Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ. Am J Physiol Regul Integr Comp Physiol 308: R238 -R249, 2015. First published December 17, 2014 doi:10.1152/ajpregu.00486.2014.-It is critical for cells to maintain a homeostatic balance of water and electrolytes because disturbances can disrupt cellular function, which can lead to profound effects on the physiology of an organism. Dehydration can be classified as either intra-or extracellular, and different mechanisms have developed to restore homeostasis in response to each. Whereas the renin-angiotensin system (RAS) is important for restoring homeostasis after dehydration, the pathways mediating the responses to intra-and extracellular dehydration may differ. Thirst responses mediated through the angiotensin type 1 receptor (AT 1R) and angiotensin type 2 receptors (AT 2R) respond to extracellular dehydration and intracellular dehydration, respectively. Intracellular signaling factors, such as protein kinase C (PKC), reactive oxygen species (ROS), and the mitogen-activated protein (MAP) kinase pathway, mediate the effects of central angiotensin II (ANG II). Experimental evidence also demonstrates the importance of the subfornical organ (SFO) in mediating some of the fluid intake effects of central ANG II. The purpose of this review is to highlight the importance of the SFO in mediating fluid intake responses to dehydration and ANG II.angiotensin; blood pressure; barin; fluid; renin FLUID BALANCE is crucial for the homeostasis and survival of organisms because they have to properly maintain fluid and electrolyte concentrations for the normal function of all cells. Fluid balance can go awry in pathological states such as in chronic kidney disease and diabetes. Among its many roles in maintaining homeostasis, the renin-angiotensin system (RAS) is an important regulator of fluid balance. The RAS achieves this through the actions of its main effector peptide, angiotensin II (ANG II) through the ANG II type 1 (AT 1 R) and type 2 (AT 2 R) receptors. Activation of AT 1 R by blood-borne ANG II in target tissues causes increases in sodium and water retention, arginine vasopressin (AVP), and aldosterone release, vasoconstriction, increased sympathetic nervous system activity, and increased fluid intake. ANG II is produced by the consecutive enzymatic action of renin on its substrate angiotensinogen (AGT) and by angiotensin-converting enzyme (ACE) on its substrate angiotensin I (ANG I). The renin-AGT cleavage step is generally the rate-limiting step in the production of ANG II, and this is certainly true in the brain where the amount of renin is limiting. The RAS exists in two forms: a circulatory form where ANG II acts as an endocrine factor, and a tissue-specific form, where local production of ANG II acts in an autocrine or paracrine manner to induce AT 1 R signaling on ANG II producing or nearby cells (75). Intracrine, or intracellular forms of the RAS, hav...

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Section: Localization Of Ras Components Required For Ang II Action: Fmentioning

confidence: 79%

Section: Stimulators Of the Brain Ras And Physiological Effects Of Sfmentioning

confidence: 99%

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Coble¹,

Grobe

Johnson³

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

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“…The DOCA-salt model (deoxycorticosterone acetate plus a high dietary sodium load) of hypertension is a well-established model of low-renin hypertension mechanistically involving brain ANG II and AT 1A receptors (16)(17)(18). It is notable that DOCAsalt also robustly stimulates RMR, an effect that also requires brain AT 1A receptors (19). However, it is not known whether RMR and BP responses are mediated by AT 1A receptors on the same population of cells in the brain.…”

Section: Resultsmentioning

confidence: 99%

“…The RMR was determined using respirometry as described previously (19,30,46,50). Briefly, mice were placed into thermally controlled, air-tight chambers maintained at thermoneutrality (30°C), and oxygen consumption and carbon dioxide content of effluent air (flowing at 300 ml/min, corrected to standard temperature and pressure) were continually recorded (AEI analyzers, logged using an ADInstruments PowerLab with the associated Chart software).…”

Section: Author Contributionsmentioning

confidence: 99%

“…BP and heart rate were assessed using radiotelemetric BP probes (DSI; model TA11PA-C10), with cannulae implanted into the common carotid artery, as previously described (19). Briefly, probes were implanted under ketamine/xylazine anesthesia, and animals were allowed to recover for at least 1 week before 3 consecutive 24-hour periods were recorded (baseline).…”

Section: Author Contributionsmentioning

confidence: 99%

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Angiotensin AT1A receptors on leptin receptor–expressing cells control resting metabolism

Claflin¹,

Sandgren²,

Lambertz³

et al. 2017

Journal of Clinical Investigation

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Central Nervous System Regulation of Brown Adipose Tissue

Morrison

Madden

2014

Comprehensive Physiology

118

103

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Thermogenesis, the production of heat energy, in brown adipose tissue is a significant component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature in many species from mouse to man and plays a key role in elevating body temperature during the febrile response to infection. The sympathetic neural outflow determining brown adipose tissue (BAT) thermogenesis is regulated by neural networks in the CNS which increase BAT sympathetic nerve activity in response to cutaneous and deep body thermoreceptor signals. Many behavioral states, including wakefulness, immunologic responses, and stress, are characterized by elevations in core body temperature to which central command-driven BAT activation makes a significant contribution. Since energy consumption during BAT thermogenesis involves oxidation of lipid and glucose fuel molecules, the CNS network driving cold-defensive and behavioral state-related BAT activation is strongly influenced by signals reflecting the short and long-term availability of the fuel molecules essential for BAT metabolism and, in turn, the regulation of BAT thermogenesis in response to metabolic signals can contribute to energy balance, regulation of body adipose stores and glucose utilization. This review summarizes our understanding of the functional organization and neurochemical influences within the CNS networks that modulate the level of BAT sympathetic nerve activity to produce the thermoregulatory and metabolic alterations in BAT thermogenesis and BAT energy expenditure that contribute to overall energy homeostasis and the autonomic support of behavior.

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Angiotensinergic Signaling in the Brain Mediates Metabolic Effects of Deoxycorticosterone (DOCA)-Salt in C57 Mice

Cited by 94 publications

References 30 publications

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Mechanisms of brain renin angiotensin system-induced drinking and blood pressure: importance of the subfornical organ

Angiotensin AT1A receptors on leptin receptor–expressing cells control resting metabolism

Central Nervous System Regulation of Brown Adipose Tissue

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