Protective effect of long-term angiotensin II inhibition

2007 ◽  
Vol 293 (3) ◽  
pp. H1351-H1358 ◽  
Author(s):  
Nidia Basso ◽  
Rosa Cini ◽  
Adriana Pietrelli ◽  
León Ferder ◽  
Norberto A. Terragno ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protective Effect ◽  
Cardiovascular System ◽  
Enzyme Inhibitor ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Experimental Period ◽  
Control Group ◽  
Ang Ii

Experimental studies indicate that angiotensin II (ANG II) through its type 1 receptor (AT1) promotes cardiovascular hypertrophy and fibrosis. Therefore, the aim of this study was to analyze whether chronic long-term inhibition of the renin-angiotensin system (RAS) can prevent most of the deleterious effects due to aging in the cardiovascular system of the normal rat. The main objective was to compare two strategies of ANG II blockade: a converting enzyme inhibitor (CEI) and an AT1 receptor blocker (AT1RB). A control group remained untreated; treatment was initiated 2 wk after weaning. A CEI, enalapril (10 mg·kg−1·day−1), or an AT1RB, losartan (30 mg·kg−1·day−1), was used to inhibit the RAS. Systolic blood pressure, body weight, and water and food intake were recorded over the whole experimental period. Heart, aorta, and mesenteric artery weight as well as histological analysis of cardiovascular structure were performed at 6 and 18 mo. Twenty animals in each of the three experimental groups were allowed to die spontaneously. The results demonstrated a significant protective effect on the function and structure of the cardiovascular system in all treated animals. Changes observed at 18 mo of age in the hearts and aortas were quite significant, but each treatment completely abolished this deterioration. The similarity between the results detected with either enalapril or losartan treatment clearly indicates that most of the effects are exerted through AT1 receptors. An outstanding finding was the significant and similar prolongation of life span in both groups of treated animals compared with untreated control animals.

Thermal responses to central angiotensin II, SQ 20881, and dopamine infusions in sheep

1985 ◽  
Vol 248 (3) ◽  
pp. R371-R377 ◽  
Author(s):  
B. S. Huang ◽  
M. J. Kluger ◽  
R. L. Malvin
Keyword(s):  
Angiotensin Ii ◽  
Body Temperature ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Significant Rise ◽  
Ang Ii ◽  
Deep Body Temperature ◽  
Angiotensin System ◽  
Conscious Sheep

The thermoregulatory role of brain angiotensin II (ANG II) was tested by intracerebroventricular (IVT) infusion of ANG II or the converting enzyme inhibitor SQ 20881 (SQ) in 15 conscious sheep. Deep body temperature decreased 0.30 +/- 0.07 degree C (SE) during the 3-h period of IVT ANG II (25 ng/min) infusion (P less than 0.05) and increased 0.50 +/- 0.13 degree C during IVT SQ (1 microgram/min) infusion (P less than 0.01). To determine whether the rise in body temperature after IVT SQ infusion might be the result of a central renin-angiotensin system (RAS), SQ was infused IVT in five conscious sheep 20 h after bilateral nephrectomy. This resulted in a significant rise in body temperature of 0.28 +/- 0.05 degree C (P less than 0.05). When vasopressin antidiuretic hormone (ADH) was infused intravenously at the same time of IVT SQ infusion, the rise in temperature was depressed, but ADH did not lower the temperature below basal. IVT dopamine (20 micrograms/min) increased body temperature by 0.40 +/- 0.04 degree C (P less than 0.01), which was qualitatively similar to the result with IVT SQ. These data support the hypothesis that endogenous brain ANG II may play a role in thermoregulation. Furthermore, plasma ADH level, regulated in part by brain ANG II, is probably not the mediator of that thermoregulation. The similar effects of IVT dopamine and SQ on body temperature strengthen the hypothesis that dopamine may be involved in the central action of brain ANG II.

Central effects of angiotensin II and dopamine in sodium-depleted sheep

1985 ◽  
Vol 248 (5) ◽  
pp. R541-R548
Author(s):  
B. S. Huang ◽  
R. L. Malvin ◽  
R. J. Grekin
Keyword(s):  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Angiotensin System ◽  
Aldosterone Level ◽  
Central Effects ◽  
Dopaminergic Pathway

The effects of intracerebroventricular (IVT) infusion of angiotensin II (ANG II), the converting enzyme inhibitor SQ 20881, and dopamine were studied in 15 conscious Na-depleted sheep. IVT ANG II (25 ng/min) significantly increased plasma aldosterone (163 +/- 24%) and vasopressin (ADH) (533 +/- 100%). Plasma renin activity (PRA) was decreased to 64 +/- 10% of basal. IVT SQ (1 microgram/min) decreased aldosterone to 70 +/- 10% and ADH to 55 +/- 9% of basal. PRA increased to 124 +/- 10%. There were no significant changes in plasma Na, K, or cortisol levels nor in mean arterial or intracranial pressure after either infusion. Increasing the dose of SQ to 10 micrograms/min resulted in an increased magnitude of change in the same variables. IVT SQ (1 microgram/min) significantly decreased aldosterone level in five nephrectomized sheep. The responses to IVT dopamine (20 micrograms/min) were qualitatively similar to those elicited by IVT SQ. These data support the existence of an endogenous brain renin-angiotensin system (RAS) independent of the renal RAS. ANG II acts centrally to regulate plasma ADH, aldosterone, and PRA levels. The similarity of the responses to SQ and dopamine suggests that a dopaminergic pathway may be involved in these responses.

scholarly journals Angiotensin-II promotes Na+ uptake in larval zebrafish, Danio rerio, in acidic and ion-poor water

2013 ◽  
Vol 220 (3) ◽  
pp. 195-205 ◽  
Author(s):  
Yusuke Kumai ◽  
Nicholas J Bernier ◽  
Steve F Perry
Keyword(s):  
Angiotensin Ii ◽  
Danio Rerio ◽  
Glucocorticoid Receptors ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Whole Body ◽  
Ang Ii ◽  
Larval Zebrafish ◽  
Rapid Activation ◽  
Stimulation Of

The contribution of the renin–angiotensin system (RAS) to Na+uptake was investigated in larval zebrafish (Danio rerio). At 4 days post fertilization (dpf), the level of whole-body angiotensin-II (ANG-II) was significantly increased after 1- or 3-h exposure to acidic (pH=4.0) or ion-poor water (20-fold dilution of Ottawa tapwater), suggesting rapid activation of the RAS. Long-term (24 h) treatment of 3 dpf larvae with ANG-I or ANG-II significantly increased Na+uptake which was accompanied by an increase in mRNA expression of the Na+-Cl−cotransporter (zslc12a10.2). Induction of Na+uptake by exposure to ANG-I was blocked by simultaneously treating larvae with lisinopril (an angiotensin-converting enzyme inhibitor). Acute (2 h) exposure to acidic water or ion-poor water led to significant increase in Na+uptake which was partially blocked by the ANG-II receptor antagonist, telmisartan. Consistent with these data, translational knockdown of renin prevented the stimulation of Na+uptake following exposure to acidic or ion-poor water. The lack of any effects of pharmacological inhibition (using RU486), or knockdown of glucocorticoid receptors on the stimulation of Na+uptake during acute exposure to acidic or ion-poor environments, indicates that the acute effects of RAS occur independently of cortisol signaling. The results of this study demonstrate that the RAS is involved in Na+homeostasis in larval zebrafish.

Control of glomerular filtration rate by circulating angiotensin II

1981 ◽  
Vol 241 (3) ◽  
pp. R190-R197 ◽  
Author(s):  
J. E. Hall ◽  
T. G. Coleman ◽  
A. C. Guyton ◽  
P. R. Kastner ◽  
J. P. Granger
Keyword(s):  
Glomerular Filtration Rate ◽  
Angiotensin Ii ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Initial Control ◽  
Arteriolar Resistance

Previous studies from our laboratory have provided evidence that the renin-angiotensin system plays an important role in controlling glomerular filtration rate (GFR) through an efferent arteriolar vasoconstrictor mechanism; however, the relative importance of circulating versus intrarenally formed angiotensin II (ANG II) in this control has not been determined. In the present study, the role of circulating ANG II in regulating GFR during reduced renal artery pressure (RAP) was examined in sodium-depleted dogs. After 90 min of infusion of the angiotensin-converting enzyme inhibitor SQ 14225, which presumably inhibited formation of both circulating and intrarenal ANG II, reduction of RAP to 81 +/- 2 mmHg resulted in marked decreases in GFR, filtration fraction (FF), and calculated efferent arteriolar resistance (RE), whereas renal blood flow (RBF) was maintained approximately 40% above initial control levels determined before SQ 14225 infusion. Replacement of circulating ANG II during SQ 14225 infusion, by intravenous infusion of ANG II at rates that decreased RBF to control levels, increased GFR, FF, and RE to levels not significantly different from control while RAP was maintained constant by aortic constriction. These observations suggest that circulating ANG II plays an important role in regulating RE and GFR during reductions in RAP. The importance of intrarenally formed ANG II in controlling GFR remains to be determined.

scholarly journals An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

2021 ◽  
Vol 12 ◽  
Author(s):  
Kanika Verma ◽  
Malvika Pant ◽  
Sarvesh Paliwal ◽  
Jaya Dwivedi ◽  
Swapnil Sharma
Keyword(s):  
Signal Transduction ◽  
Angiotensin Ii ◽  
Cardiovascular System ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
System A ◽  
Receptor Signal ◽  
Ras Family ◽  
Regulated Functions

The multifaceted nature of the renin-angiotensin system (RAS) makes it versatile due to its involvement in pathogenesis of the cardiovascular disease. Angiotensin II (Ang II), a multifaceted member of RAS family is known to have various potential effects. The knowledge of this peptide has immensely ameliorated after meticulous research for decades. Several studies have evidenced angiotensin I receptor (AT1 R) to mediate the majority Ang II-regulated functions in the system. Functional crosstalk between AT1 R mediated signal transduction cascades and other signaling pathways has been recognized. The review will provide an up-to-date information and recent discoveries involved in Ang II receptor signal transduction and their functional significance in the cardiovascular system for potential translation in therapeutics. Moreover, the review also focuses on the role of stem cell-based therapies in the cardiovascular system.

Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system

2007 ◽  
Vol 292 (1) ◽  
pp. C82-C97 ◽  
Author(s):  
Puja K. Mehta ◽  
Kathy K. Griendling
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular System ◽  
G Protein ◽  
Focal Adhesion ◽  
Tyrosine Kinases ◽  
Vascular Function ◽  
Map Kinases ◽  
Renin Angiotensin System ◽  
Central Component ◽  
Ang Ii

The renin-angiotensin system is a central component of the physiological and pathological responses of cardiovascular system. Its primary effector hormone, angiotensin II (ANG II), not only mediates immediate physiological effects of vasoconstriction and blood pressure regulation, but is also implicated in inflammation, endothelial dysfunction, atherosclerosis, hypertension, and congestive heart failure. The myriad effects of ANG II depend on time (acute vs. chronic) and on the cells/tissues upon which it acts. In addition to inducing G protein- and non-G protein-related signaling pathways, ANG II, via AT1 receptors, carries out its functions via MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases [PDGF, EGFR, insulin receptor], and nonreceptor tyrosine kinases [Src, JAK/STAT, focal adhesion kinase (FAK)]. AT1R-mediated NAD(P)H oxidase activation leads to generation of reactive oxygen species, widely implicated in vascular inflammation and fibrosis. ANG II also promotes the association of scaffolding proteins, such as paxillin, talin, and p130Cas, leading to focal adhesion and extracellular matrix formation. These signaling cascades lead to contraction, smooth muscle cell growth, hypertrophy, and cell migration, events that contribute to normal vascular function, and to disease progression. This review focuses on the structure and function of AT1 receptors and the major signaling mechanisms by which angiotensin influences cardiovascular physiology and pathology.

Rapid elicitation of salt appetite by an intravenous infusion of angiotensin II in rats

1996 ◽  
Vol 270 (5) ◽  
pp. R1092-R1098 ◽  
Author(s):  
D. A. Fitts ◽  
R. L. Thunhorst
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Intravenous Infusion ◽  
Enzyme Inhibitor ◽  
Direct Action ◽  
Renin Angiotensin System ◽  
Salt Appetite ◽  
Ang Ii ◽  
Direct Stimulation ◽  
Arterial Blood

A role for the renal renin-angiotensin system in the direct stimulation of salt appetite in the rat remains controversial because attempts to elicit the behavior by intravenous administration of angiotensin II (ANG II) have been unconvincing. We recently demonstrated that depletion-induced salt appetite was attenuated by selective blockade of peripheral ANG II synthesis with an intravenous dose of converting enzyme inhibitor [captopril (Cap)] that does not block the synthesis of ANG II inside the blood brain barrier. We now show that intravenous ANG II at 30 ng/min rapidly reestablishes salt appetite in Cap-blocked rats. The mean arterial blood pressure (MAP) of unblocked, sodium-depleted rats was normal, but Cap-blocked, depleted rats had low MAP. An intravenous infusion of ANG II in Cap-blocked rats brought MAP into the normal range and elicited water and salt drinking within 90 min. Phenylephrine also normalized MAP but failed to elicit fluid intake in Cap-blocked, sodium-deficient rats. Sodium and water balances tended to be more positive during ANG II than during phenylephrine infusions. Thus circulating ANG II may stimulate both thirst and salt appetite by a direct action on the brain and not by causing natriuresis or by raising the blood pressure.

scholarly journals Central AT1 receptor signaling by circulating angiotensin II is permissive to acute intermittent hypoxia-induced sympathetic neuroplasticity

2020 ◽  
Vol 128 (5) ◽  
pp. 1329-1337
Author(s):  
Caroline G. Shimoura ◽  
Mary Ann Andrade ◽  
Glenn M. Toney
Keyword(s):  
Angiotensin Ii ◽  
Intermittent Hypoxia ◽  
Renin Angiotensin System ◽  
Time Dependent ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Angiotensin System ◽  
Ras Activation ◽  
Long Term Facilitation

Acute intermittent hypoxia (AIH) triggers sympathetic long-term facilitation (sLTF) that relies on peripheral renin-angiotensin system (RAS) activation. Here, increasing AIH cycles from 5 to 10 proportionally increased RAS activity, but not the magnitude of post-AIH sLTF. Brain angiotensin II (ANG II) receptor blockade and nephrectomy each largely prevented sLTF, whereas central ANG II rescued it following nephrectomy. Peripheral RAS activation by AIH induces time-dependent neuroplasticity at an apparent central ANG II signaling threshold, triggering a stereotyped sLTF response.

Chronic endothelin-induced pressor and renal actions in conscious dogs do not require altered ANG II formation

1995 ◽  
Vol 268 (2) ◽  
pp. R395-R402 ◽  
Author(s):  
F. C. Wilkins ◽  
S. Kassab ◽  
T. Kato ◽  
H. L. Mizelle ◽  
T. J. Opgenorth ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Filtration Rate ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Important Interaction ◽  
Circulating Levels

Plasma endothelin levels are elevated approximately two- to threefold in a number of chronic pathophysiological conditions associated with hypertension. Results from recent studies indicate an important interaction between endothelin and the renin-angiotensin system (RAS). The role of the RAS in mediating the increases in arterial pressure produced by long-term pathophysiological elevations in circulating levels of endothelin is unknown. Therefore, the purpose of this study was to chronically increase circulating levels of endothelin within the pathophysiological range and determine the long-term cardiovascular and renal actions of endothelin in control dogs (n = 6) and in dogs pretreated with a converting-enzyme inhibitor (CEI) (n = 6) or CEI + angiotensin II (ANG II) replacement (n = 6). Infusion of endothelin-1 for 8 days at a rate of 2.5 ng.kg-1.min-1 increased plasma endothelin from 7.1 +/- 0.9 to 19.8 +/- 3.3 pg/ml. In control dogs, endothelin increased mean arterial pressure (MAP) by 19% (90 +/- 2 to 107 +/- 3 mmHg) while decreasing renal blood flow (RBF) by 30% and glomerular filtration rate (GFR) by 15-20%. Long-term elevation of circulating endothelin produced similar elevations in MAP in dogs pretreated with CEI (+16%) or CEI + ANG II (+17%). Similar decreases in RBF and GFR also occurred in response to endothelin in all three groups. These results indicate that although long-term increases in circulating endothelin within the pathophysiological range produce significant increases in arterial pressure, this effect does not appear to be mediated by the RAS.

Losartan and Angiotensin II Inhibit Aldosterone Production in Anephric Rats via Different Actions on the Intraadrenal Renin-Angiotensin System*

Endocrinology ◽  
1999 ◽  
Vol 140 (2) ◽  
pp. 675-682 ◽  
Author(s):  
Jörg Peters ◽  
Nicholas Obermüller ◽  
Alexander Woyth ◽  
Barbara Peters ◽  
Christiane Maser-Gluth ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Latency Period ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Relative Contribution ◽  
Aldosterone Production

Abstract Angiotensin II (ANG II) is a major stimulator of aldosterone biosynthesis. When investigating the relative contribution of circulating and locally produced ANG II, we were therefore surprised to find that ANG II, given chronically sc (200 ng/kg·min), markedly inhibits a nephrectomy (NX)-induced rise of aldosterone concentrations (from 10 ± 2 to 465 ± 90 ng/100 ml in vehicle infused, and from 9 ± 2 to 177 ± 35 in ANG II infused rats 55 h after NX and hemodialysis). We further observed, by in situ hybridization, that bilateral NX increases the number of adrenocortical cells expressing renin and that this rise was prevented by ANG II. Moreover, the rise of aldosterone levels was also inhibited by the AT1-receptor antagonist, losartan (10 μg/kg·min, chronically ip from 8 ± 2 to 199 ± 26 ng/100 ml), despite the absence of circulating renin and a reduction of ANG I to less than 10%. These data demonstrate that aldosterone production, after NX, is regulated by an intraadrenal renin-angiotensin system and that this system is physiologically suppressed by circulating angiotensin. Because the effects of losartan or ANG II on aldosterone production involved a latency period of at least 30 h after NX and were associated with a modulation or recruitment of renin-producing cells, we suggest that the intraadrenal renin-angiotensin system operates via regulation of cell differentiation on a long-term scale, rather than or additionally to its short-term effects on aldosterone synthase activity.

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