Cardiac Physiology and the Renin Angiotensin System: Lessons from Transgenic Animal Models

2006 ◽  
pp. 19-30
Author(s):  
Alisdair Ryding ◽  
John J. Mullins
Keyword(s):  
Animal Models ◽  
Renin Angiotensin System ◽  
Transgenic Animal ◽  
Cardiac Physiology ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Transgenic Animal Models

scholarly journals Increased (pro)renin receptor expression in the subfornical organ of hypertensive humans

2018 ◽  
Vol 314 (4) ◽  
pp. H796-H804 ◽  
Author(s):  
Silvana G. Cooper ◽  
Darshan P. Trivedi ◽  
Rieko Yamamoto ◽  
Caleb J. Worker ◽  
Cheng-Yuan Feng ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Animal Models ◽  
Systolic Blood Pressure ◽  
Renin Angiotensin System ◽  
Subfornical Organ ◽  
Antihypertensive Drug Therapy ◽  
Angiotensin System ◽  
Human Hypertension ◽  
Renin Angiotensin ◽  
The Brain

The central nervous system plays an important role in essential hypertension in humans and in animal models of hypertension through modulation of sympathetic activity and Na+ and body fluid homeostasis. Data from animal models of hypertension suggest that the renin-angiotensin system in the subfornical organ (SFO) of the brain is critical for hypertension development. We recently reported that the brain (pro)renin receptor (PRR) is a novel component of the brain renin-angiotensin system and could be a key initiator of the pathogenesis of hypertension. Here, we examined the expression level and cellular distribution of PRR in the SFO of postmortem human brains to assess its association with the pathogenesis of human hypertension. Postmortem SFO tissues were collected from hypertensive and normotensive human subjects. Immunolabeling for the PRR and a retrospective analysis of clinical data were performed. We found that human PRR was prominently expressed in most neurons and microglia, but not in astrocytes, in the SFO. Importantly, PRR levels in the SFO were elevated in hypertensive subjects. Moreover, PRR immunoreactivity was significantly correlated with systolic blood pressure but not body weight, age, or diastolic blood pressure. Interestingly, this correlation was independent of antihypertensive drug therapy. Our data indicate that PRR in the SFO may be a key molecular player in the pathogenesis of human hypertension and, as such, could be an important focus of efforts to understand the neurogenic origin of hypertension. NEW & NOTEWORTHY This study provides evidence that, in the subfornical organ of the human brain, the (pro)renin receptor is expressed in neurons and microglia cells but not in astrocytes. More importantly, (pro)renin receptor immunoreactivity in the subfornical organ is increased in hypertensive humans and is significantly correlated with systolic blood pressure.

Chronic Renin-Angiotensin System Activation Induced Neuroinflammation: Common Mechanisms Underlying Hypertension and Dementia?

2021 ◽  
pp. 1-13
Author(s):  
Shirley Tran ◽  
Sanjaya Kuruppu ◽  
Niwanthi W. Rajapakse
Keyword(s):  
Cognitive Impairment ◽  
Angiotensin Ii ◽  
Animal Models ◽  
Vascular Dementia ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Current Evidence ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Chronic Activation

Hypertension is a major risk factor for the pathogenesis of vascular dementia and Alzheimer’s disease. Chronic activation of the renin-angiotensin system (RAS) contributes substantially to neuroinflammation. We propose that neuroinflammation arising from chronic RAS activation can initiate and potentiate the onset of hypertension and related dementia. Neuroinflammation induced by chronic activation of the RAS plays a key role in the pathogenesis of dementia. Increased levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and transforming growth factor (TGF)-β have been reported in brain tissue of vascular dementia patients and animal models of vascular dementia induced by either angiotensin II infusion or transverse aortic coarctation. It is proposed that neuronal cell death and synaptic dysfunction induced by neuroinflammation lead to cognitive impairment in dementia. The neuroprotective RAS pathway, regulated by angiotensin-converting enzyme 2 (ACE2) which converts angiotensin II into angiotensin-(1–7), can attenuate hypertension and dementia. Furthermore, the use of anti-hypertensive medications in preventing dementia or cognitive decline in hypertensive patients and animal models of dementia have mostly been beneficial. Current evidence suggests a strong link between RAS induced neuroinflammation and the onset of hypertension and dementia, which warrants further investigation. Strategies to counteract an overactive RAS and enhance the neuroprotective arm of the RAS may help prevent or improve cognitive impairment associated with hypertension.

Involvement of the renin–angiotensin system in abdominal and thoracic aortic aneurysms

2012 ◽  
Vol 123 (9) ◽  
pp. 531-543 ◽  
Author(s):  
Hong Lu ◽  
Debra L. Rateri ◽  
Dennis Bruemmer ◽  
Lisa A. Cassis ◽  
Alan Daugherty
Keyword(s):  
Animal Models ◽  
Aortic Rupture ◽  
Association Studies ◽  
Renin Angiotensin System ◽  
Pharmacological Therapy ◽  
Aortic Aneurysms ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Thoracic Aortic Aneurysms

Aortic aneurysms are relatively common maladies that may lead to the devastating consequence of aortic rupture. AAAs (abdominal aortic aneurysms) and TAAs (thoracic aortic aneurysms) are two common forms of aneurysmal diseases in humans that appear to have distinct pathologies and mechanisms. Despite this divergence, there are numerous and consistent demonstrations that overactivation of the RAS (renin–angiotensin system) promotes both AAAs and TAAs in animal models. For example, in mice, both AAAs and TAAs are formed during infusion of AngII (angiotensin II), the major bioactive peptide in the RAS. There are many proposed mechanisms by which the RAS initiates and perpetuates aortic aneurysms, including effects of AngII on a diverse array of cell types and mediators. These experimental findings are complemented in humans by genetic association studies and retrospective analyses of clinical data that generally support a role of the RAS in both AAAs and TAAs. Given the lack of a validated pharmacological therapy for any form of aortic aneurysm, there is a pressing need to determine whether the consistent findings on the role of the RAS in animal models are translatable to humans afflicted with these diseases. The present review compiles the recent literature that has shown the RAS as a critical component in the pathogenesis of aortic aneurysms.

scholarly journals (Pro)renin receptor and V-ATPase: from Drosophila to humans

2013 ◽  
Vol 126 (8) ◽  
pp. 529-536 ◽  
Author(s):  
Anthony Rousselle ◽  
Gabin Sihn ◽  
Martijn Rotteveel ◽  
Michael Bader
Keyword(s):  
Gene Deletion ◽  
Renin Angiotensin System ◽  
Transgenic Animal ◽  
Specific Gene ◽  
Developmental Studies ◽  
Cellular Functions ◽  
Angiotensin System ◽  
Transgenic Animal Models ◽  
Canonical Wnt

A decade ago, the (P)RR [(pro)renin receptor] was discovered and depicted as a potential activator of the tissue renin–angiotensin system. For this reason, the role of the (P)RR in cardiovascular diseases and diabetes has been particularly studied. However, the discovery of embryonic lethality after (P)RR gene deletion in mouse and zebrafish paved the way for additional roles of (P)RR in cell homoeostasis. Indeed, the (P)RR has been shown to associate with vacuolar H+-ATPase, hence its other name ATP6ap2. Developmental studies in Xenopus and Drosophila have revealed an essential role of this association to promote the canonical and non-canonical Wnt signalling pathways, whereas studies with tissue-specific gene deletion have pointed out a role in autophagy. The present review aims to summarize recent findings on the cellular functions of (P)RR emerging from various mutated and transgenic animal models.

The role of the renin-angiotensin system in the pathogenesis of Parkinson’s disease

2021 ◽  
pp. 107-115
Author(s):  
Ю.Н. Быков ◽  
Н.А. Тетюшкин ◽  
В.А. Чипизубов ◽  
А.Н. Калягин ◽  
С.Ю. Лаврик
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Neurological Disorders ◽  
Renin Angiotensin System ◽  
Dopamine Level ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin

Введение. В настоящее время в научной литературе имеется большой объем данных, посвященных болезни Паркинсона. В то же время недостаточно освещена роль ренин-ангиотензиновой системы (РАС) в патогенезе заболевания. Цель - оценка современных патогенетически обоснованных подходов к терапии болезни Паркинсона. Методика. В базах данных Medline (PubMed) и eLibrary осуществлен подбор и анализ современных источников литературы, посвященных изучению роли ренин-ангиотензиновой системы в патогенезе болезни Паркинсона. Результаты. Болезнь Паркинсона является хроническим нейродегенеративным заболеванием, которое проявляется моторными и немоторными нарушениями. Анализ литературы показал, что помимо системной ренин-ангиотензиновой системы во многих тканях и органах имеется локальная РАС. Авторами было показано, что дофамин и ангиотензин II взаимодействуют в черной субстанции (SN) и стриатуме в реципрокном отношении. В модельных экспериментах на животных доказано, что снижение уровней дофамина сопровождается гиперактивацией ренин-ангиотензиновой системы. При этом так же отмечается выброс активных форм кислорода, индуцируемый микроглиальной тканью, и развитие нейровоспаления, что сопровождается нейродегенерацией. Применение блокаторов ангиотензиновых рецепторов в моделях на животных и в клинических испытаниях позволило значительно снизить прогрессирование нейродегенерации черной субстанции. Заключение. Авторами изложены результаты, свидетельствующие о том, что развитие болезни Паркинсона сопровождается гиперактивацией мозговой РАС. Подразумевается, что на новое звено патогенеза можно терапевтически воздействовать. Необходимы дополнительные исследования для понимания механизмов данных процессов. Background. A large amount of literature on Parkinson’s disease is currently available. However, the role of the renin-angiotensin system in the pathogenesis of this disease is not sufficiently covered. Aim. To highlight new therapeutic possibilities based on pathophysiological mechanisms of Parkinson’s disease. Methods. The literature retrieved from the PubMed, Medline, and eLibrary databases focusing on the role of the renin-angiotensin system in the pathogenesis of Parkinson’s disease was analyzed. Results. Parkinson’s disease (PD) is a chronic neurodegenerative disease associated with persistent neurological disorders. Studies have demonstrated that a local renin-angiotensin system (RAS) exists in many tissues and organs along with the systemic RAS. The authors showed that dopamine and angiotensin II interact reciprocally in the substantia nigra (SN) and striatum. In animal models, a decrease in the dopamine level was accompanied by RAS overactivation. Furthermore, microglial tissue induced production of reactive oxygen species, which was associated with neuroinflammation. The angiotensin receptor blocker treatment used in animal models and clinical trials significantly reduced the progression of SN neurodegeneration. Conclusions. The authors reviewed the data of literature demonstrating that the progression of Parkinson’s disease is associated with overactivation of the cerebral RAS. Apparently, it is possible to influence therapeutically this new pathogenetic component of Parkinson’s disease. Further study is required for understanding the mechanisms of this process.

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