scholarly journals Angiotensin-(1-7) Central Mechanisms After ICV Infusion in Hypertensive Transgenic (mRen2)27 Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Lucas M. Kangussu ◽  
Marcella Nunes Melo-Braga ◽  
Bruna Soares de Souza Lima ◽  
Robson A. S. Santos ◽  
Hélida Monteiro de Andrade ◽  
...  

Graphical AbstractHypothalamic mechanisms induced by ICV infusion of angiotensin-(1-7) in the transgenic (mRen2)27 hypertensive animals. Ang-(1-7) treatment modulated components of the renin-angiotensin system (RAS), attenuating increased levels of AT1 and ACE activity, and negatively modulated inflammatory profile, by increasing anti-inflammatory IL-10 and decreasing TNFα and iNOS in the hypothalamus. Further, altered oxidative stress/inflammation by ROS mediator, decreasing Uchl1 (ubiquitin carboxyl-terminal hydrolase isozyme L1) while increasing antioxidant peroxiredoxin 1 (figure was created with pictures from biorender.com).

2002 ◽  
Vol 30 (01) ◽  
pp. 87-93 ◽  
Author(s):  
Dae Gill Kang ◽  
Yong Gab Yun ◽  
Jang Hyun Ryoo ◽  
Ho Sub Lee

A study was designed to elucidate the mechanism of anti-hypertensive effects of Danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of Danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of Danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of Danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed. The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of Danshen extract for three weeks. These results suggest that Danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.


2020 ◽  
Vol 71 (6) ◽  
pp. 307-311
Author(s):  
Sorin Ungurianu ◽  
Constantin Trus ◽  
Roxana-Rosmary Enciu

It is already known from a variety of previous reports that an independent brain renin�angiotensin system (RAS) exists, completely separated from the one in the periphery. This independent brain RAS has all the precursors and the enzymatic structures necessary for the generation of the angiotensin peptides. Thus, in the last few years various groups started focusing on the more central effects of less known angiotensins (e.g in comparison with Angiotensin (Ang) II), namely Ang III, Ang IV, Ang-(1�7) or Ang 5-8. One of these newly emerging angiotensins which has become an increased center of interest in many studies is Ang-(1-7), which is a heptapeptide previously described especially for its opposite effects to Ang II, in the peripheral vascular area, but also described for some opposite central functions vs. Ang II. These aspects are completed with the fact that it was recently suggested that the renin�angiotensin system could modulate the oxidative stress metabolism, and also it seems that the manifestations of Angiotensin-(1-7) on the basal oxidative stress status are contradictory, with a variety of reports describing controversial (e.g. both pro-oxidant and antioxidant actions) effects for this heptapeptide. Our results presented here are confirming a possible antioxidant effect of Ang-(1�7) administration on rat, as shown by the increased levels of antioxidant enzymes from the temporal lobe (superoxide dismutase and glutathione peroxidase) and decreased levels of malondialdehyde, as an important lipid peroxidation parameter.


2017 ◽  
Vol 1863 (5) ◽  
pp. 1106-1114 ◽  
Author(s):  
Latha Ramalingam ◽  
Kalhara Menikdiwela ◽  
Monique LeMieux ◽  
Jannette M. Dufour ◽  
Gurvinder Kaur ◽  
...  

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ying Ma ◽  
Yu-Ming Kang* ◽  
Zhi-Ming Yang ◽  
Joseph Francis*

Introduction: Neurohumoral mechanisms play an important role in the pathophysiology of congestive heart failure (HF). Recent studies suggest that the brain renin angiotensin system (RAS) plays an important role in regulating body fluids and sympathetic drive in HF. In addition, it has been shown that there is cross talk between cytokines and RAS in cardiovascular disease. In this study we determined whether blockade of brain RAS attenuate inflammatory cytokines and oxidative stress in HF rats. Methods and Results: Adult male Sprague-Dawley rats were implanted with intracerebroventricular (ICV) cannulae and subjected to coronary artery ligation to induce HF and confirmed by echocardiography. Rats were treated with an angiotensin type 1 receptors (AT1-R) antagonist losartan (LOS, 20 μg/hr, ICV) or vehicle (VEH) for 4 weeks. At the end of the study, left ventricular (LV) function was measured by echocardiography and rats were sacrificed, and brain and plasma samples were collected for measurements of cytokines and superoxide using immunohistochemistry, Western blot and real time RT-PCR. HF rats induced significant increases in Nuclear Factor-kappaB (NF-κB) p50-positive neurons and activated microglia in the paraventricular nucleus (PVN) of hypothalamus, and TNF-α, IL-1β, IL-6 and NF-κB p50 in hypothalamus when compared with sham rats. These animals also had increased staining for dihydroethidium (DHE) and plasma levels of norepinephrine (NE), an indirect indicator of sympathetic activity. In contrast, ICV treatment with LOS attenuated cytokine expression and oxidative stress in the PVN and hypothalamus when compared with VEH treated HF rats. ICV treatment with LOS also reduced plasma NE levels, and proinflammatory cytokine, heart weight to body weight ratio with decreased LV end-diastolic pressure. Conclusions : These findings suggest the cross talk between the cytokines and renin angiotensin system within the brain contribute to sympatho-excitation in HF.


2020 ◽  
Vol 27 (6) ◽  
pp. 463-475 ◽  
Author(s):  
Lucas M. Kangussu ◽  
Lucas Alexandre Santos Marzano ◽  
Cássio Ferraz Souza ◽  
Carolina Couy Dantas ◽  
Aline Silva Miranda ◽  
...  

Cerebrovascular Diseases (CVD) comprise a wide spectrum of disorders, all sharing an acquired or inherited alteration of the cerebral vasculature. CVD have been associated with important changes in systemic and tissue Renin-Angiotensin System (RAS). The aim of this review was to summarize and to discuss recent findings related to the modulation of RAS components in CVD. The role of RAS axes is more extensively studied in experimentally induced stroke. By means of AT1 receptors in the brain, Ang II hampers cerebral blood flow and causes tissue ischemia, inflammation, oxidative stress, cell damage and apoptosis. On the other hand, Ang-(1-7) by stimulating Mas receptor promotes angiogenesis in brain tissue, decreases oxidative stress, neuroinflammation, and improves cognition, cerebral blood flow, neuronal survival, learning and memory. In regard to clinical studies, treatment with Angiotensin Converting Enzyme (ACE) inhibitors and AT1 receptor antagonists exerts preventive and therapeutic effects on stroke. Besides stroke, studies support a similar role of RAS molecules also in traumatic brain injury and cerebral aneurysm. The literature supports a beneficial role for the alternative RAS axis in CVD. Further studies are necessary to investigate the therapeutic potential of ACE2 activators and/or Mas receptor agonists in patients with CVD.


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