Inhibition of the renin–angiotensin system prevents seizures in a rat model of epilepsy

2010 ◽  
Vol 119 (11) ◽  
pp. 477-482 ◽  
Author(s):  
Marilia G.A.G. Pereira ◽  
Christiane Becari ◽  
José A.C. Oliveira ◽  
Maria Cristina O. Salgado ◽  
Norberto Garcia-Cairasco ◽  
...  
Keyword(s):  
Rat Model ◽  
Hormone Secretion ◽  
Renin Angiotensin System ◽  
Epileptic Seizures ◽  
At1 Receptor ◽  
Electrolyte Balance ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Central Nervous System

The RAS (renin–angiotensin system) is classically involved in BP (blood pressure) regulation and water–electrolyte balance, and in the central nervous system it has been mostly associated with homoeostatic processes, such as thirst, hormone secretion and thermoregulation. Epilepsies are chronic neurological disorders characterized by recurrent epileptic seizures that affect 1–3% of the world's population, and the most commonly used anticonvulsants are described to be effective in approx. 70% of the population with this neurological alteration. Using a rat model of epilepsy, we found that components of the RAS, namely ACE (angiotensin-converting enzyme) and the AT1 receptor (angiotensin II type 1 receptor) are up-regulated in the brain (2.6- and 8.2-fold respectively) following repetitive seizures. Subsequently, epileptic animals were treated with clinically used doses of enalapril, an ACE inhibitor, and losartan, an AT1 receptor blocker, leading to a significant decrease in seizure severities. These results suggest that centrally acting drugs that target the RAS deserve further investigation as possible anticonvulsant agents and may represent an additional strategy in the management of epileptic patients.

Activation of the GLP-1 Receptor by Liraglutide Increases ACE2 Expression, Reversing Right Ventricle Hypertrophy, and Improving the Production of SP-A and SP-B in the Lungs of Type 1 Diabetes Rats

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3559-3569 ◽  
Author(s):  
Marina Romaní-Pérez ◽  
Verónica Outeiriño-Iglesias ◽  
Christian M. Moya ◽  
Pilar Santisteban ◽  
Lucas C. González-Matías ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Right Ventricle ◽  
Rat Model ◽  
Renin Angiotensin System ◽  
Surfactant Protein ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ventricle Hypertrophy ◽  
Right Ventricle Hypertrophy

Diabetes alters microvascular function in the vascular beds of organs, including the lungs. Cardiovascular complications of pulmonary vascular affectation may be a consequence of the overactivation of the vasoconstrictive and proliferative components of the renin-angiotensin system. We previously reported that pulmonary physiology and surfactant production is improved by the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide (LIR) in a rat model of lung hypoplasia. Because we hypothesized that streptozotocin-induced diabetes rats would show deficiencies in lung function, including surfactant proteins, and develop an imbalance of the renin-angiotensin system in the lungs. This effect would in turn be prevented by long-acting agonists of the GLP-1R, such as LIR. The induction of diabetes reduced the surfactant protein A and B in the lungs and caused the vasoconstrictor component of the renin-angiotensin system to predominate, which in turn increased angiotensin II levels, and ultimately being associated with right ventricle hypertrophy. LIR restored surfactant protein levels and reversed the imbalance in the renin-angiotensin system in this type 1 diabetes mellitus rat model. Moreover, LIR provoked a strong increase in angiotensin-converting enzyme 2 expression in the lungs of both diabetic and control rats, and in the circulating angiotensin(1–7) in diabetic animals. These effects prompted complete reversion of right ventricle hypertrophy. The consequences of LIR administration were independent of glycemic control and of glucocorticoids, and they involved NK2 homeobox 1 signaling. This study demonstrates by first time that GLP-1R agonists, such as LIR, might improve the cardiopulmonary complications associated with diabetes.

Endogenous angiotensin II in the NTS contributes to sympathetic activation in rats with aortocaval shunt

2001 ◽  
Vol 280 (6) ◽  
pp. R1665-R1673 ◽  
Author(s):  
Hideaki Shigematsu ◽  
Yoshitaka Hirooka ◽  
Kenichi Eshima ◽  
Miwako Shihara ◽  
Tatsuya Tagawa ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Urinary Catecholamine ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Aortocaval Shunt ◽  
The Central Nervous System ◽  
High Output

Recent studies have suggested that the central nervous system is responsible for activation of sympathetic nerve activity (SNA) and the renin-angiotensin system in heart failure (HF). The aim of this study was to determine whether activation of the renin-angiotensin system within the nucleus of the solitary tract (NTS) plays a role in enhanced SNA in HF. High-output HF was induced by an aortocaval (A-V) shunt with some modifications in the rat. These rats exhibited a left ventricular dilatation and hemodynamic signs of high-output HF. Urinary catecholamine excretion and maximal renal SNA (RSNA) were greater in the A-V shunted rats than in the control rats. Microinjection of an angiotensin II type 1-receptor antagonist, CV11974, into the NTS was performed. The arterial pressure and RSNA were reduced by CV11974 to a greater degree in the A-V shunted rats than in the control rats. The expression of angiotensin-converting enzyme mRNA in the medulla was greater in the A-V shunted rats than in the control rats. These results suggest that activation of the renin-angiotensin system within the NTS contributes to an enhanced SNA in this model.

UPREGULATION OF RENIN ANGIOTENSIN SYSTEM IN TYPE 1 DIABETES MELLITUS ASSOCIATED WITH HYPERTENSION

2011 ◽  
Vol 29 ◽  
pp. e377-e378
Author(s):  
L. Morais ◽  
I. Watanabe ◽  
M. Franco ◽  
D. Arita ◽  
M. Gabbay ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

Erythropoietin during hypoglycaemia in type 1 diabetes: Relation to basal renin-angiotensin system activity and cognitive function

2009 ◽  
Vol 85 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Peter Lommer Kristensen ◽  
Thomas Høi-Hansen ◽  
Niels Vidiendal Olsen ◽  
Ulrik Pedersen-Bjergaard ◽  
Birger Thorsteinsson
Keyword(s):  
Type 1 Diabetes ◽  
Cognitive Function ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
System Activity ◽  
Renin Angiotensin

scholarly journals Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels

2021 ◽  
Author(s):  
Kinga Jaworska ◽  
Mateusz Koper ◽  
Marcin Ufnal
Keyword(s):  
Gut Microbiota ◽  
Renin Angiotensin System ◽  
Gastrointestinal Diseases ◽  
Electrolyte Balance ◽  
Ample Evidence ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
System A ◽  
Potential Mediator ◽  
The One

Gut microbiota is a potent biological modulator of many physiological and pathological states. The renin-angiotensin system (RAS), including the local gastrointestinal RAS (GI RAS), emerges as a potential mediator of microbiota-related effects. The RAS is involved in cardiovascular system homeostasis, water-electrolyte balance, intestinal absorption, glycemic control, inflammation, carcinogenesis and aging-related processes. Ample evidence suggests a bidirectional interaction between the microbiome and RAS. On the one hand, gut bacteria and their metabolites may modulate GI and systemic RAS. On the other hand, changes in the intestinal habitat caused by alterations in RAS may shape microbiota metabolic activity and composition. Notably, the pharmacodynamic effects of the RAS-targeted therapies may be in part mediated by the intestinal RAS and changes in the microbiome. This review summarizes studies on gut microbiota and RAS physiology. Expanding the research on this topic may lay a foundation for new therapeutic paradigms in gastrointestinal diseases and multiple systemic disorders.

Abstract 227: The Protective Effect of Kidney-Specific ACE Inhibition Against Chronic Angiotensin II Infusions is Associated with Blunted Intrarenal Renin-Angiotensin System Activation

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Jorge F Giani ◽  
Tea Djandjoulia ◽  
Nicholas Fetcher ◽  
Sebastien Fuchs ◽  
Dale M Seth ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Fold Increase ◽  
Ace Inhibition ◽  
Sham Operation ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Intrarenal Ras ◽  
Failed Induction

Introduction: The responses to chronic angiotensin (Ang) II infusions of gene-targeted mice lacking kidney angiotensin-converting enzyme (ACE), in terms of intrarenal Ang II accumulation, hypertension, sodium and water retention are all blunted or absent. The objective of this study was to determine if these reduced responses were associated with changes in the intrarenal renin-angiotensin system (RAS). METHODS: Mice lacking intrarenal ACE (ACE10/10) were generated by targeted homologous recombination placing the expression of ACE only in macrophages. As a result, these mice have normal circulating ACE levels, but no kidney ACE. Wild-type (WT) mice of the same background (C57Bl/J) served as controls. Mice were subjected to sham-operation or subcutaneous infusion of Ang II for two weeks (n=6-10, 400 ng/kg/min via osmotic minipump). Mean arterial pressure (MAP) was followed by telemetry. At the end of the experiment, the kidneys were collected for analysis. Ang II content was measured by RIA. Renal abundance of ACE, angiotensinogen (AGT) and Ang II receptor type 1 (AT1R) were determined by Western Blot in total kidney homogenates. Results: At baseline, the MAP of WT and ACE 10/10 mice was similar 110 ± 4 mmHg vs. 109 ± 3 mmHg respectively (p>0.05). However, when subjected to chronic Ang II infusions, the hypertensive response was blunted in ACE 10/10 mice (129 ± 6 mmHg) vs. WT (146 ± 5 mmHg; P<0.05). Also, intrarenal Ang II accumulation was lower in ACE10/10 mice (724 ± 81 fmol/g) vs. WT (1130 ± 105 fmol/g, p<0.05). In non-treated mice, intrarenal RAS components analysis revealed that the absence of ACE in ACE10/10 mice was accompanied by a significant reduction in AGT (0.41 ± 0.06) and increased AT1R expression (1.32 ± 0.05) when compared to WT (normalized to 1.00, p<0.05 in both instances). Importantly, after chronic Ang II infusions, AGT, ACE and AT1R expression increased in WT (1.36, 1.26 and 1.17 fold increase respectively compared to non-treated WT, p<0.05) but not in the ACE10/10 mice (1.19, 1.06, 0.89 fold increase respectively compared to non-treated ACE10/10, p>0.05). Conclusion: The blunted hypertension and Ang II accumulation of mice devoid of kidney ACE in response to Ang II infusions is associated with a failed induction of renal AGT and the AT1R.

The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment

2007 ◽  
Vol 292 (5) ◽  
pp. H2523-H2531 ◽  
Author(s):  
Steven J. Miller ◽  
Laura E. Norton ◽  
Michael P. Murphy ◽  
Michael C. Dalsing ◽  
Joseph L. Unthank
Keyword(s):  
Renin Angiotensin System ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin ◽  
Growth Impairment ◽  
Collateral Growth ◽  
Collateral Artery

Recent clinical and animal studies have shown that collateral artery growth is impaired in the presence of vascular risk factors, including hypertension. Available evidence suggests that angiotensin-converting enzyme inhibitors (ACEI) promote collateral growth in both hypertensive humans and animals; however, the specific mechanisms are not established. This study evaluated the hypothesis that collateral growth impairment in hypertension is mediated by excess superoxide produced by NAD(P)H oxidase in response to stimulation of the ANG II type 1 receptor. After ileal artery ligation, mesenteric collateral growth did not occur in untreated, young, spontaneously hypertensive rats. Significant luminal expansion occurred in collaterals of spontaneously hypertensive rats treated with the superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and the ACEI captopril, but not ANG II type 1 (losartan) or type 2 (PD-123319) receptor blockers. The ACEI enalapril produced equivalent reduction of arterial pressure as captopril but did not promote luminal expansion. This suggests the effects of captopril on collateral growth might result from its antioxidant properties. RT-PCR demonstrated that ANG II type 1 receptor and angiotensinogen expression was reduced in collaterals of untreated rats. This local suppression of the renin angiotensin system provides a potential explanation for the lack of effect of enalapril and losartan on collateral growth. The results demonstrate the capability of antioxidant therapies, including captopril, to reverse impaired collateral artery growth and the novel finding that components of the local renin angiotensin system are naturally suppressed in collaterals.

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