scholarly journals An evolving story of angiotensin-II-forming pathways in rodents and humans

2013 ◽  
Vol 126 (7) ◽  
pp. 461-469 ◽  
Author(s):  
Carlos Maria Ferrario ◽  
Sarfaraz Ahmad ◽  
Sayaka Nagata ◽  
Stephen W. Simington ◽  
Jasmina Varagic ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Left Atrial ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Lessons Learned ◽  
The Novel ◽  
Angiotensin System ◽  
Ventricular Tissue ◽  
Made In

Lessons learned from the characterization of the biological roles of Ang-(1–7) [angiotensin-(1–7)] in opposing the vasoconstrictor, proliferative and prothrombotic actions of AngII (angiotensin II) created an underpinning for a more comprehensive exploration of the multiple pathways by which the RAS (renin–angiotensin system) of blood and tissues regulates homoeostasis and its altered state in disease processes. The present review summarizes the progress that has been made in the novel exploration of intermediate shorter forms of angiotensinogen through the characterization of the expression and functions of the dodecapeptide Ang-(1–12) [angiotensin-(1–12)] in the cardiac production of AngII. The studies reveal significant differences in humans compared with rodents regarding the enzymatic pathway by which Ang-(1–12) undergoes metabolism. Highlights of the research include the demonstration of chymase-directed formation of AngII from Ang-(1–12) in human left atrial myocytes and left ventricular tissue, the presence of robust expression of Ang-(1–12) and chymase in the atrial appendage of subjects with resistant atrial fibrillation, and the preliminary observation of significantly higher Ang-(1–12) expression in human left atrial appendages.

A Review of Angiotensin Receptor Blocker-based Therapies at all Levels of Cardiovascular Risk

2011 ◽  
Vol 7 (4) ◽  
pp. 254 ◽  
Author(s):  
Giuliano Tocci ◽  
Lorenzo Castello ◽  
Massimo Volpe ◽  
◽  
◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ventricular Hypertrophy ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Clinical Settings ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Receptor Blockers ◽  
Artery Disease

The renin–angiotensin system (RAS) has a key role in the maintenance of cardiovascular homeostasis, and water and electrolyte metabolism in healthy subjects, as well as in several diseases including hypertension, left ventricular hypertrophy and dysfunction, coronary artery disease, renal disease and congestive heart failure. These conditions are all characterised by abnormal production and activity of angiotensin II, which represents the final effector of the RAS. Over the last few decades, accumulating evidence has demonstrated that antihypertensive therapy based on angiotensin II receptor blockers (ARBs) has a major role in the selective antagonism of the main pathological activities of angiotensin II. Significant efforts have been made to demonstrate that blocking the angiotensin II receptor type 1 (AT1) subtype receptors through ARB-based therapy results in proven benefits in different clinical settings. In this review, we discuss the main benefits of antihypertensive strategies based on ARBs in terms of their efficacy, safety and tolerability.

scholarly journals Effects of inhibition of the renin-angiotensin system on hypertension-induced target organ damage: clinical and experimental evidence

2021 ◽  
Vol 91 (1) ◽  
Author(s):  
Maria Rosaria De Luca ◽  
Daniela Sorriento ◽  
Domenico Massa ◽  
Valeria Valente ◽  
Federica De Luise ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ace Inhibitors ◽  
Ventricular Hypertrophy ◽  
Target Organ Damage ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Left Ventricular ◽  
Target Organ ◽  
Angiotensin System ◽  
Hypertensive Patients

The dysregulation of renin-angiotensin-system (RAS) plays a pivotal role in hypertension and in the development of the related target organ damage (TOD). The main goal of treating hypertension is represented by the long-term reduction of cardiovascular (CV) risk. RAS inhibition either by angiotensin converting enzyme (ACE)-inhibitors or by type 1 Angiotensin II receptors blockers (ARBs), reduce the incidence of CV events in hypertensive patients. Actually, ACE-inhibitors and ARBs have been demonstrated to be effective to prevent, or delay TOD like left ventricular hypertrophy, chronic kidney disease, and atherosclerosis. The beneficial effects of RAS blockers on clinical outcome of hypertensive patients are due to the key role of angiotensin II in the pathogenesis of TOD. In particular, Angiotensin II through an inflammatory-mediated mechanism plays a role in the initiation, progression and vulnerability of atherosclerotic plaque. In addition, Angiotensin II can be considered the hormonal transductor of the pressure overload in cardiac myocytes, and through an autocrine-paracrine mechanism plays a role in the development of left ventricular hypertrophy. Angiotensin II by modulating the redox status and the immune system participates to the development of chronic kidney disease. The RAS blocker should be considered the first therapeutic option in patients with hypertension, even if ACE-inhibitors and ARBs have different impact on CV prevention. ARBs seem to have greater neuro-protective effects, while ACE-inhibitors have greater cardio-protective action.

Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats

1990 ◽  
Vol 259 (2) ◽  
pp. H324-H332 ◽  
Author(s):  
K. M. Baker ◽  
M. I. Chernin ◽  
S. K. Wixson ◽  
J. F. Aceto
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Abdominal Aorta ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Angiotensin I ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Nuclease Mapping

We have recently shown that the octapeptide angiotensin II is a potent stimulus of protein synthesis and growth in cultured cardiomyocytes. The present study was performed to determine if the renin-angiotensin system was involved in regulating cardiac cell growth in vivo. The pressure-overload cardiac hypertrophy model that develops in abdominal aorta-constricted rats was studied. At 7 and 15 days after abdominal aorta constriction, rats developed significant left ventricular hypertrophy. The increase in left ventricular mass was completely prevented in animals fed the angiotensin-converting enzyme inhibitor, enalapril maleate (0.2 mg/ml) in their drinking water. Cardiac afterload was the same in both groups of animals in that carotid artery pressures were not different in conscious awake aortic-constricted animals receiving and not receiving enalapril. These data suggest a direct growth effect of angiotensin II on the left ventricle and indicate a role for the renin-angiotensin system in the cardiac hypertrophy that develops in response to pressure overload. The presence and chamber localization of angiotensinogen mRNA was determined using Northern hybridization and S1 nuclease mapping analysis. Angiotensinogen mRNA, as determined by dot-blot hybridization analysis, was significantly increased in hypertrophied left ventricles at both 7 and 15 days after the surgery, when compared with sham-operated controls. The activity of the circulating renin-angiotensin system, as indexed by plasma renin activity was increased at 1 day following surgery [6.0 +/- 2.0 ng.ml-1.h-1 angiotensin I (control) vs. 41.8 +/- 10.9 ng.ml-1.h-1 angiotensin I (experimental)], but returned to control values by day 3 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Teaching aldosterone regulation and basic scientific principles using a classic paper by Dr. James O. Davis and colleagues

2006 ◽  
Vol 30 (4) ◽  
pp. 141-144 ◽  
Author(s):  
Craig J. Hanke ◽  
Angela C. Bauer-Dantoin
Keyword(s):  
Angiotensin Ii ◽  
Effective Means ◽  
Renin Angiotensin System ◽  
Zona Glomerulosa ◽  
Angiotensin System ◽  
Quantitative Measurements ◽  
Scientific Principles ◽  
Hypothalamic Pituitary Axis ◽  
Classic Paper

Classroom discussion of scientific articles can be an effective means of teaching scientific principles and methodology to both undergraduate and graduate science students. The availability of classic papers from the American Physiological Society Legacy Project has made it possible to access articles dating back to the early portions of the 20th century. In this article, we discuss a classic paper from the laboratory of Dr. James O. Davis on the regulation of aldosterone synthesis from the adrenal zona glomerulosa cell. Dr. Davis has conducted much of the seminal research investigating the renin-angiotensin system and the regulation of aldosterone release by angiotensin II. In addition to a characterization of the effects of ACTH on aldosterone regulation, this study is useful for discussing the basic principles of negative feedback pathways of the hypothalamic-pituitary axis. This study also provides examples of early bioassay techniques for the detection of angiotensin II and of the importance of quantitative measurements when investigating physiological responses. Three figures and one table are reproduced from the original article along with a series of discussion questions designed to facilitate discovery learning.

Chronic administration of angiotensin II receptor antagonist, TCV-116, in cardiomyopathic hamsters

1994 ◽  
Vol 267 (6) ◽  
pp. H2297-H2304 ◽  
Author(s):  
F. Nakamura ◽  
M. Nagano ◽  
R. Kobayashi ◽  
J. Higaki ◽  
H. Mikami ◽  
...  
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Cardiac Dysfunction ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Lv Function ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
At1 Antagonist

We examined whether specific blockade of the renin-angiotensin system is beneficial for the treatment of cardiac dysfunction in heart failure. The angiotensin II type-1 (AT1) receptor antagonist TCV-116 (10 mg.kg-1.day-1) or its vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were significantly higher in CM than in GS hamsters. The CM heart showed a smaller response of left ventricular (LV) pressure and first derivative of maximal LV pressure (+dP/dtmax) to the elevation of perfusion pressure (from 60 to 120 cmH2O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not affect LV function in GS but significantly improved cardiac contractility in CM hamsters. These results suggest that the renin-angiotensin system plays an important role in the development of cardiac dysfunction due to cardiomyopathy. Blockade of this system by the AT1 antagonist TCV-116 appears to be useful in the prevention of heart failure.

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.

Renin-angiotensin system inhibition on noradrenergic nerve terminal function in pacing-induced heart failure

2000 ◽  
Vol 279 (6) ◽  
pp. H3012-H3019 ◽  
Author(s):  
Hiroya Kawai ◽  
Suzanne Y. Stevens ◽  
Chang-Seng Liang
Keyword(s):  
Heart Failure ◽  
Angiotensin Ii ◽  
Nerve Terminal ◽  
Sympathetic Nerve ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Left Ventricular ◽  
Cardiac Sympathetic Nerve ◽  
Angiotensin System ◽  
Sympathetic Nerve Terminal

Chronic angiotensin-converting enzyme (ACE) inhibition has been shown to improve cardiac sympathetic nerve terminal function in heart failure. To determine whether similar effects could be produced by angiotensin II AT1 receptor blockade, we administered the ACE inhibitor quinapril, angiotensin II AT1 receptor blocker losartan, or both agents together, to rabbits with pacing-induced heart failure. Chronic rapid pacing produced left ventricular dilation and decline of fractional shortening, increased plasma norepinephrine (NE), and caused reductions of myocardial NE uptake activity, NE histofluorescence profile, and tyrosine hydroxylase immunostained profile. Administration of quinapril or losartan retarded the progression of left ventricular dysfunction and attenuated cardiac sympathetic nerve terminal abnormalities in heart failure. Quinapril and losartan together produced greater effects than either agent alone. The effect of renin-angiotensin system inhibition on improvement of left ventricular function and remodeling, however, was not sustained. Our results suggest that the effects of ACE inhibitors are mediated via the reduction of angiotensin II and that angiotensin II plays a pivotal role in modulating cardiac sympathetic nerve terminal function during development of heart failure. The combined effect of ACE inhibition and angiotensin II AT1 receptor blockade on cardiac sympathetic nerve terminal dysfunction may contribute to the beneficial effects on cardiac function in heart failure.

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