scholarly journals Controlled Hemorrhage Sensitizes Angiotensin II-Elicited Hypertension through Activation of the Brain Renin-Angiotensin System Independently of Endoplasmic Reticulum Stress

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Guo-Biao Wu ◽  
Hui-Bo Du ◽  
Jia-Yi Zhai ◽  
Si Sun ◽  
Jun-Ling Cui ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protein Expression ◽  
Plasma Levels ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Phenylbutyric Acid ◽  
The Brain

Hemorrhagic shock is associated with activation of renin-angiotensin system (RAS) and endoplasmic reticulum stress (ERS). Previous studies demonstrated that central RAS activation produced by various challenges sensitizes angiotensin (Ang) II-elicited hypertension and that ERS contributes to the development of neurogenic hypertension. The present study investigated whether controlled hemorrhage could sensitize Ang II-elicited hypertension and whether the brain RAS and ERS mediate this sensitization. Results showed that hemorrhaged (HEM) rats had a significantly enhanced hypertensive response to a slow-pressor infusion of Ang II when compared to sham HEM rats. Treatment with either angiotensin-converting enzyme (ACE) 1 inhibitor, captopril, or ACE2 activator, diminazene, abolished the HEM-induced sensitization of hypertension. Treatment with the ERS agonist, tunicamycin, in sham HEM rats also sensitized Ang II-elicited hypertension. However, blockade of ERS with 4-phenylbutyric acid in HEM rats did not alter HEM-elicited sensitization of hypertension. Either HEM or ERS activation produced a greater reduction in BP after ganglionic blockade, upregulated mRNA and protein expression of ACE1 in the hypothalamic paraventricular nucleus (PVN), and elevated plasma levels of Ang II but reduced mRNA expression of the Ang-(1-7) receptor, Mas-R, and did not alter plasma levels of Ang-(1-7). Treatment with captopril or diminazene, but not phenylbutyric acid, reversed these changes. No treatments had effects on PVN protein expression of the ERS marker glucose-regulated protein 78. The results indicate that controlled hemorrhage sensitizes Ang II-elicited hypertension by augmenting RAS prohypertensive actions and reducing RAS antihypertensive effects in the brain, which is independent of ERS mechanism.

Influence of brain renin-angiotensin system on renal sympathetic and cardiac baroreflexes in conscious rabbits

1991 ◽  
Vol 260 (3) ◽  
pp. H770-H778 ◽  
Author(s):  
P. K. Dorward ◽  
C. D. Rudd
Keyword(s):  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Transient Pressure ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Before And After ◽  
Conscious Rabbits ◽  
The Brain ◽  
Renal Sympathetic

The role of the brain renin-angiotensin system (RAS) in the baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) was studied in conscious rabbits. RSNA and HR were recorded during slow ramp changes in mean arterial pressure (MAP) before and after intraventricular infusion of 1) angiotensin II (ANG II), 2) ANG II receptor antagonist, [Sar1,Ile8]ANG II, or 3) converting enzyme inhibitor (CEI, enalaprilat). Central ANG II increased resting MAP and RSNA by 10.6 +/- 0.9 mmHg and 21 +/- 7%, respectively, but did not alter HR. There was a marked increase of 107 +/- 15% in the maximum RSNA evoked by slowly lowering MAP. In contrast, maximum reflex tachycardia was only modestly elevated, and baroreflex inhibition of RSNA and HR during MAP rises was unaffected. Central [Sar1,Ile8]ANG II had no effect on RSNA or HR, either at rest or during baroreflex responses, while CEI slightly enhanced maximal reflex responses. Thus exogenous ANG II causes a powerful excitation of renal sympathetic motoneurons, the magnitude of which is revealed when tonic baroreceptor inhibition is removed during transient pressure falls. However, in quietly resting conscious rabbits, we found no evidence for a tonic influence of endogenous ANG II on these neurons, and the physiological stimuli required for their activation by the brain RAS remain to be found.

scholarly journals The Prorenin and (Pro)renin Receptor: New Players in the Brain Renin-Angiotensin System?

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wencheng Li ◽  
Hua Peng ◽  
Dale M. Seth ◽  
Yumei Feng
Keyword(s):  
Renin Angiotensin System ◽  
Ang Ii ◽  
Future Perspectives ◽  
Vasopressin Release ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Treatment Of Hypertension ◽  
High Level ◽  
The Brain

It is well known that the brain renin-angiotensin (RAS) system plays an essential role in the development of hypertension, mainly through the modulation of autonomic activities and vasopressin release. However, how the brain synthesizes angiotensin (Ang) II has been a debate for decades, largely due to the low renin activity. This paper first describes the expression of the vasoconstrictive arm of RAS components in the brain as well as their physiological and pathophysiological significance. It then focus on the (pro)renin receptor (PRR), a newly discovered component of the RAS which has a high level in the brain. We review the role of prorenin and PRR in peripheral organs and emphasize the involvement of brain PRR in the pathogenesis of hypertension. Some future perspectives in PRR research are heighted with respect to novel therapeutic target for the treatment of hypertension and other cardiovascular diseases.

Role of tissue renin angiotensin system in two-kidney, one-clip hypertensive rats

1993 ◽  
Vol 264 (3) ◽  
pp. F510-F514
Author(s):  
R. Morishita ◽  
J. Higaki ◽  
H. Okunishi ◽  
F. Nakamura ◽  
M. Nagano ◽  
...  
Keyword(s):  
Mrna Level ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Ang Ii ◽  
Gene Expressions ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Significant Difference ◽  
Renin Mrna ◽  
The Brain

To investigate the molecular pathology of two-kidney, one-clip (2K-1C) rats, we examined the gene expressions of the renin-angiotensin system (RAS) and angiotensin II (ANG II) concentration in various tissues in the early (4 wk) and chronic (16 wk) phases of hypertension. Four weeks after clipping, the brain renin mRNA level was lower in 2K-1C rats than in control rats (P < 0.05). On the other hand, the levels of brain and renal angiotensinogen mRNA were not significantly different in the two groups. The brain and adrenal ANG II concentrations were significantly higher in 2K-1C rats than in control rats. Sixteen weeks after clipping, there was no significant difference in the brain renin mRNA levels in the two groups, and renal and brain angiotensinogen mRNA levels were normal. Moreover, the ANG II concentrations in the adrenals and brain (except the cortex) of 2K-1C rats were not significantly higher than those in control rats. These results show a differential pattern of tissue RAS gene expression in rats during the development of 2K-1C hypertension, which is regulated in a tissue-specific manner. Furthermore, the data suggest that brain ANG II may be affected by circulating ANG II, but not by the brain renin angiotensin system, and may regulate brain renin, probably by negative feedback through its own receptor.

Coronary vasoconstrictor influence of angiotensin II is reduced in remodeled myocardium after myocardial infarction

2006 ◽  
Vol 291 (5) ◽  
pp. H2082-H2089 ◽  
Author(s):  
Daphne Merkus ◽  
David B. Haitsma ◽  
Oana Sorop ◽  
Frans Boomsma ◽  
Vincent J. de Beer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Plasma Levels ◽  
Vascular Tone ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Volume Blood ◽  
Coronary Vasoconstrictor

The renin-angiotensin system plays an important role in cardiovascular homeostasis by contributing to the regulation of blood volume, blood pressure, and vascular tone. Because AT1 receptors have been described in the coronary microcirculation, we investigated whether ANG II contributes to the regulation of coronary vascular tone and whether its contribution is altered during exercise. Since the renin-angiotensin system is activated after myocardial infarction, resulting in an increase in circulating ANG II, we also investigated whether the contribution of ANG II to the regulation of vasomotor tone is altered after infarction. Twenty-six chronically instrumented swine were studied at rest and while running on a treadmill at 1–4 km/h. In 13 swine, myocardial infarction was induced by ligation of the left circumflex coronary artery. Blockade of AT1 receptors (irbesartan, 1 mg/kg iv) had no effect on myocardial O2 consumption but resulted in an increase in coronary venous O2 tension and saturation both at rest and during exercise, reflecting coronary vasodilation. Despite increased plasma levels of ANG II after infarction and maintained coronary arteriolar AT1 receptor levels, the vasodilation evoked by irbesartan was significantly reduced both at rest and during exercise. In conclusion, despite elevated plasma levels, the vasoconstrictor influence of ANG II on the coronary circulation in vivo is reduced after myocardial infarction. This reduction in ANG II-induced coronary vasoconstriction may serve to maintain perfusion of the remodeled myocardium.

scholarly journals The ACE2/Angiotensin-(1–7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1–7)

2018 ◽  
Vol 98 (1) ◽  
pp. 505-553 ◽  
Author(s):  
Robson Augusto Souza Santos ◽  
Walkyria Oliveira Sampaio ◽  
Andreia C. Alzamora ◽  
Daisy Motta-Santos ◽  
Natalia Alenina ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Renin Angiotensin System ◽  
The Body ◽  
Biologically Active ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Past ◽  
The Brain ◽  
System Focus

The renin-angiotensin system (RAS) is a key player in the control of the cardiovascular system and hydroelectrolyte balance, with an influence on organs and functions throughout the body. The classical view of this system saw it as a sequence of many enzymatic steps that culminate in the production of a single biologically active metabolite, the octapeptide angiotensin (ANG) II, by the angiotensin converting enzyme (ACE). The past two decades have revealed new functions for some of the intermediate products, beyond their roles as substrates along the classical route. They may be processed in alternative ways by enzymes such as the ACE homolog ACE2. One effect is to establish a second axis through ACE2/ANG-(1–7)/MAS, whose end point is the metabolite ANG-(1–7). ACE2 and other enzymes can form ANG-(1–7) directly or indirectly from either the decapeptide ANG I or from ANG II. In many cases, this second axis appears to counteract or modulate the effects of the classical axis. ANG-(1–7) itself acts on the receptor MAS to influence a range of mechanisms in the heart, kidney, brain, and other tissues. This review highlights the current knowledge about the roles of ANG-(1–7) in physiology and disease, with particular emphasis on the brain.

scholarly journals The brain renin-angiotensin system and cardiovascular responses to stress: insights from transgenic rats with low brain angiotensinogen

2012 ◽  
Vol 113 (12) ◽  
pp. 1929-1936 ◽  
Author(s):  
Amy C. Arnold ◽  
Atsushi Sakima ◽  
Sherry O. Kasper ◽  
Sherry Vinsant ◽  
Maria Antonia Garcia-Espinosa ◽  
...  
Keyword(s):  
Stress Responses ◽  
Renin Angiotensin System ◽  
Cardiovascular Responses ◽  
Ang Ii ◽  
Transgenic Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Brain Peptides ◽  
The Impact ◽  
The Brain

The renin-angiotensin system (RAS) has been identified as an attractive target for the treatment of stress-induced cardiovascular disorders. The effects of angiotensin (ANG) peptides during stress responses likely result from an integration of actions by circulating peptides and brain peptides derived from neuronal and glial sources. The present review focuses on the contribution of endogenous brain ANG peptides to pathways involved in cardiovascular responses to stressors. During a variety of forms of stress, neuronal pathways in forebrain areas containing ANG II or ANG-(1–7) are activated to stimulate descending angiotensinergic pathways that increase sympathetic outflow to increase blood pressure. We provide evidence that glia-derived ANG peptides influence brain AT1 receptors. This appears to result in modulation of the responsiveness of the neuronal pathways activated during stressors that elevate circulating ANG peptides to activate brain pathways involving descending hypothalamic projections. It is well established that increased cardiovascular reactivity to stress is a significant predictor of hypertension and other cardiovascular diseases. This review highlights the importance of understanding the impact of RAS components from the circulation, neurons, and glia on the integration of cardiovascular responses to stressors.

scholarly journals The Brain Renin-Angiotensin System and Mitochondrial Function: Influence on Blood Pressure and Baroreflex in Transgenic Rat Strains

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Manisha Nautiyal ◽  
Amy C. Arnold ◽  
Mark C. Chappell ◽  
Debra I. Diz
Keyword(s):  
Blood Pressure ◽  
Signaling Pathways ◽  
Mitochondrial Function ◽  
Renin Angiotensin System ◽  
Normal Blood ◽  
Ang Ii ◽  
Normal Blood Pressure ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Brain

Mitochondrial dysfunction is implicated in many cardiovascular diseases, including hypertension, and may be associated with an overactive renin-angiotensin system (RAS). Angiotensin (Ang) II, a potent vasoconstrictor hormone of the RAS, also impairs baroreflex and mitochondrial function. Most deleterious cardiovascular actions of Ang II are thought to be mediated by NADPH-oxidase- (NOX-) derived reactive oxygen species (ROS) that may also stimulate mitochondrial oxidant release and alter redox-sensitive signaling pathways in the brain. Within the RAS, the actions of Ang II are counterbalanced by Ang-(1–7), a vasodilatory peptide known to mitigate against increased oxidant stress. A balance between Ang II and Ang-(1–7) within the brain dorsal medulla contributes to maintenance of normal blood pressure and proper functioning of the arterial baroreceptor reflex for control of heart rate. We propose that Ang-(1–7) may negatively regulate the redox signaling pathways activated by Ang II to maintain normal blood pressure, baroreflex, and mitochondrial function through attenuating ROS (NOX-generated and/or mitochondrial).

scholarly journals The Angiotensin II Type 2 Receptor in Brain Functions: An Update

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Marie-Odile Guimond ◽  
Nicole Gallo-Payet
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Brain Functions ◽  
Physiological Relevance ◽  
Ang Iv ◽  
The Brain

Angiotensin II (Ang II) is the main active product of the renin-angiotensin system (RAS), mediating its action via two major receptors, namely, the Ang II type 1 (AT1) receptor and the type 2 (AT2) receptor. Recent results also implicate several other members of the renin-angiotensin system in various aspects of brain functions. The first aim of this paper is to summarize the current state of knowledge regarding the properties and signaling of the AT2receptor, its expression in the brain, and its well-established effects. Secondly, we will highlight the potential role of the AT2receptor in cognitive function, neurological disorders and in the regulation of appetite and the possible link with development of metabolic disorders. The potential utility of novel nonpeptide selective AT2receptor ligands in clarifying potential roles of this receptor in physiology will also be discussed. If confirmed, these new pharmacological tools should help to improve impaired cognitive performance, not only through its action on brain microcirculation and inflammation, but also through more specific effects on neurons. However, the overall physiological relevance of the AT2receptor in the brain must also consider the Ang IV/AT4receptor.

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