ORCID Profile
0000-0003-0602-8779
Current Organisation
University of Bristol
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Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.BRAINRES.2008.09.046
Abstract: Renin plays a critical role in fluid and electrolyte homeostasis by cleaving angiotensinogen to produce Ang peptides. Whilst it has been demonstrated that renin mRNA is expressed in the brain, the distribution of cells responsible for this expression remains uncertain. We have used a transgenic mouse approach in an attempt to address this question. A transgenic mouse, in which a 12.2 kb fragment of the human renin promoter was used to drive expression of Cre-recombinase, was crossed with the ROSA26-lac Z reporter mouse strain. Cre-recombinase mediated excision of the floxed stop cassette resulted in expression of the reporter protein, beta-galactosidase. This study describes the distribution of beta-galactosidase in the brain of the crossed transgenic mouse. In all cases where it was examined the reporter protein was co-localized with the neuronal marker NeuN. An extensive distribution was observed with numerous cells labeled in the somatosensory, insular, piriform and retrosplenial cortices. The motor cortex was devoid of labeled cells. Several other regions were labeled including the parts of the amygdala, periaqueductal gray, lateral parabrachial nucleus and deep cerebellar nuclei. Overall the distribution shows little overlap with those regions that are known to express receptors for the renin-angiotensin system in the adult brain. This transgenic approach, which demonstrates the distribution of cells which have activated the human renin promoter at any time throughout development, yields a unique and extensive distribution of putative renin-expressing neurons. Our observations suggest that renin may have broader actions in the brain and may indicate a potential for interaction with the (pro)renin receptor or production of a ligand for non-AT(1)/AT(2) receptors.
Publisher: Springer Science and Business Media LLC
Date: 19-09-2014
DOI: 10.1007/S11906-014-0493-1
Abstract: Hypertension is a leading risk factor for the development of several cardiovascular diseases. As the global prevalence of hypertension increases, so too has the recognition of resistant hypertension. Whilst figures vary, the proportion of hypertensive patients that are resistant to multiple drug therapies have been reported to be as high as 16.4 %. Resistant hypertension is typically associated with elevated sympathetic activity and abnormal homeostatic reflex control and is termed neurogenic hypertension because of its presumed central autonomic nervous system origin. This resistance to conventional pharmacological treatment has stimulated a plethora of medical devices to be investigated for use in hypertension, with varying degrees of success. In this review, we discuss a new therapy for drug-resistant hypertension, deep brain stimulation. The utility of deep brain stimulation in resistant hypertension was first discovered in patients with concurrent neuropathic pain, where it lowered blood pressure and improved baroreflex sensitivity. The most promising central target for stimulation is the ventrolateral periaqueductal gray, which has been well characterised in animal studies as a control centre for autonomic outflow. In this review, we will discuss the promise and potential mechanisms of deep brain stimulation in the treatment of severe, resistant hypertension.
Publisher: Wiley
Date: 05-01-2015
Publisher: Wiley
Date: 07-12-2015
DOI: 10.1113/JP271253
Publisher: S. Karger AG
Date: 2009
DOI: 10.1159/000197863
Abstract: Angiotensin II acts through specific receptors to alter several brain functions including fluid and electrolyte control, neuroendocrine function and autonomic efferent activity. This review discusses one brain site, the rostral ventrolateral medulla, where the actions of angiotensin II have been intensively studied. The rostral ventrolateral medulla plays a critical role in the generation and regulation of sympathetic activity to the cardiovascular system and hence is important for blood pressure control. Current evidence indicates that angiotensin II activates neurons in the rostral ventrolateral medulla via the AT sub A /sub receptor. In some models of cardiovascular disease, blockade of AT sub /sub receptors in the rostral ventrolateral medulla reduces sympathetic nerve activity and blood pressure suggesting that overactivity of the angiotensin system in this nucleus may play a role in the maintenance of high blood pressure.
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.AUTNEU.2013.01.010
Abstract: Following its generation by both systemic and tissue-based renin-angiotensin systems, angiotensin II interacts with specific, G-protein coupled receptors to modulate multiple physiological systems, including the cardiovascular system. Genetic models in which the different components of the renin-angiotensin system have been deleted show large changes in resting blood pressure. Interruption of the generation of angiotensin II, or its interaction with these receptors, decreases blood pressure in hypertensive humans and experimental animal models of hypertension. Whilst the interaction of angiotensin II with the kidney is pivotal in this modulation of blood pressure, an involvement of the system in other tissues is important. Both systemic angiotensins, acting via the blood-brain barrier deficient circumventricular organs, and centrally-generated angiotensin modulate cardiovascular control by regulating fluid and electrolyte ingestion, autonomic activity and neuroendocrine function. This review discusses the pathways in the brain that are involved in this regulation of blood pressure as well as examining the sites in which altered angiotensin function might contribute to the development and maintenance of high blood pressure.
Publisher: Wiley
Date: 09-12-2020
DOI: 10.1113/JP277293
Publisher: Wiley
Date: 22-08-2011
DOI: 10.1111/J.1471-4159.2011.07406.X
Abstract: Astrocytes are the major source of angiotensinogen in the brain and play an important role in the brain renin-angiotensin system. Regulating brain angiotensinogen production alters blood pressure and fluid and electrolyte homeostasis. In turn, several physiological and pathological manipulations alter expression of angiotensinogen in brain. Surprisingly, little is known about the factors that regulate astrocytic expression of angiotensinogen. There is evidence that angiotensinogen production in both hepatocytes and cardiac myocytes can be positively regulated via the angiotensin type 1 receptor, but this effect has not yet been studied in astrocytes. Therefore, the aim of this project was to establish whether angiotensin II modulates angiotensinogen production in brain astrocytes. Primary astrocyte cultures, prepared from neonatal C57Bl6 mice, expressed angiotensinogen measured by immunocytochemistry and real-time PCR. Using a variety of approaches we were unable to identify angiotensin receptors on cultured astrocytes. Exposure of cultured astrocytes to angiotensin II also did not affect angiotensinogen expression. When astrocyte cultures were transduced with the angiotensin type 1A receptor, using adenoviral vectors, angiotensin II induced a robust down-regulation (91.4% ± 1.8%, p < 0.01, n = 4) of angiotensinogen gene expression. We conclude that receptors for angiotensin II are present in extremely low levels in astrocytes, and that this concurs with available data in vivo. The signaling pathways activated by the angiotensin type 1A receptor are negatively coupled to angiotensinogen expression and represent a powerful pathway for decreasing expression of this protein, potentially via signaling pathways coupled to Gα(q/11) .
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Erin O'Callaghan.