scholarly journals Inhibitory Effects of a Subdepressor Dose of L-158,809, an Angiotensin II Type 1 Receptor Antagonist, on Cardiac Hypertrophy and Nephropathy Via the Activated Human Renin-Angiotensin System in Double Transgenic Mice With Hypertension

1998 ◽  
Vol 62 (8) ◽  
pp. 599-603 ◽  
Author(s):  
Tatsuya Kai ◽  
Keiichi Sugimura ◽  
Seijiro Shimada ◽  
Atsuhiro Kurooka ◽  
Toshihiko Takenaka ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Receptor Antagonist ◽  
Renin Angiotensin System ◽  
Inhibitory Effects ◽  
Angiotensin System ◽  
Human Renin ◽  
Double Transgenic Mice

scholarly journals Cardiac hypertrophy in mice submitted to a swimming protocol: influence of training volume and intensity on myocardial renin-angiotensin system

2019 ◽  
Vol 316 (6) ◽  
pp. R776-R782 ◽  
Author(s):  
Douglas dos Santos Soares ◽  
Graziela Hünning Pinto ◽  
Amanda Lopes ◽  
Daniel Sturza Lucas Caetano ◽  
Thaiane Gomes Nascimento ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Renin Angiotensin System ◽  
Oxidative Capacity ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Angiotensin Peptides ◽  
Physiological Cardiac Hypertrophy ◽  
Pathological Hypertrophy

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1–7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male Balb/c mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain β-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.

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 Angiotensin II Type 1 Receptor Antagonist, YM358, on Cardiac Hypertrophy and Dysfunction after Myocardial Infarction in Rats

2002 ◽  
Vol 25 (7) ◽  
pp. 857-860 ◽  
Author(s):  
Tomoko Tokioka-Akagi ◽  
Akira Fujimori ◽  
Masayuki Shibasaki ◽  
Yasuko Matsuda-Satoh ◽  
Osamu Inagaki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Receptor Antagonist

Abstract 037: Transient Cardiac Expression Of Constitutively Active G alpha Q Activates Renin-angiotensin System, Leading To Progressive Heart Failure And Ventricular Arrhythmias In Transgenic Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Naoko Matsushita ◽  
Masamichi hirose ◽  
Yasuchika Taeishi ◽  
Satoshi Suzuki ◽  
Toshihide Kashihara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Ventricular Arrhythmias ◽  
Renin Angiotensin System ◽  
Gene Expressions ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Progressive Heart Failure ◽  
Constitutively Active

Introduction: Transgenic mice with transient cardiac expression of constitutively active Galpha q (Gαq-TG) caused progressive heart failure and ventricular arrhythmias after the initiating stimulus becomes undetectable. However, the mechanisms are still unknown. Renin-angiotensin system plays a critical role in the development of cardiac hypertrophy and heart failure. We examined the effects of chronic administration of olmesartan on ventricular function, the number of premature ventricular contractions (PVC), and ventricular remodeling in Gαq-TG mice. Methods and Results: Olmesartan (1 mg/kg/day) or vehicle was chronically administered to Gαq-TG from 6 to 32 weeks of age, and all experiments were performed in mice at the age of 32 weeks. Chronic olmesartan treatment prevented the severe reduction of left ventricular fractional shortening and inhibited ventricular interstitial fibrosis and ventricular myocyte hypertrophy in Gαq-TG. Electrocardiogram demonstrated that premature ventricular contraction (PVC) was frequently (more than 20 beats/min) observed in 9 of 10 vehicle-treated Gαq-TG but in none of 10 olmesartan -treated Gαq-TG. The QT interval was significantly shorter in olmesartan-treated Gαq-TG than vehicle-treated Gαq-TG. CTGF, collagen type 1, ANP, BNP, and β-MHC gene expression was increased in vehicle-treated Gαq-TG. Olmesartan significantly decreased these gene expressions in Gαq-TG. Moreover, protein expressions of canonical transient receptor potential (TRPC) channels 3 and 6 increased in vehicle-treated Gαq-TG hearts. Olmesartan significantly decreased TRPC6 expressions in Gαq-TG. Angiotensin converting enzyme (ACE) 1 and 2 gene expressions were also increased in vehicle-treated Gαq-TG and was not decreased to the control level in olmesartan-treated Gαq-TG. Conclusions: These findings suggest that renin-angiotensin system has an important role in the development of cardiac hypertrophy and heart failure even if the initiating stimulus is different from the activation of renin-angiotensin system.

scholarly journals Renin-Angiotensin System Blockers and the COVID-19 Pandemic

Hypertension ◽  
2020 ◽  
Vol 75 (6) ◽  
pp. 1382-1385 ◽  
Author(s):  
A.H. Jan Danser ◽  
Murray Epstein ◽  
Daniel Batlle
Keyword(s):  
Angiotensin Ii ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Receptor Blockers ◽  
Renin Angiotensin System Blockers

During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly. Many of those patients are treated with renin-angiotensin system blockers. Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection. The present article discusses this concept. ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects. In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.

Inhibitory effects of candesartan on responses to angiotensin peptides in the hindquarters vascular bed of the cat

1998 ◽  
Vol 76 (2) ◽  
pp. 133-140 ◽  
Author(s):  
David G Lambert ◽  
Hunter C Champion ◽  
Philip J Kadowitz
Keyword(s):  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
High Dose ◽  
Inhibitory Effects ◽  
Angiotensin Peptides ◽  
Vascular Bed ◽  
Angiotensin Iii ◽  
The Right ◽  
Dose Dependent

The effects of the nonpeptide angiotensin II AT1 receptor antagonist candesartan on responses to angiotensin II were investigated in the hindquarters vascular bed of the cat. Under constant-flow conditions, injections of angiotensin II into the hindquarters perfusion circuit elicited dose-dependent increases in perfusion pressure. Candesartan in a dose of 3 µg/kg iv decreased vasoconstrictor responses to angiotensin II in a competitive manner. However, at doses of 10-1000 µg/kg iv, candesartan shifted the dose-response curve to angiotensin II to the right in a nonparallel manner, suggesting a noncompetitive blockade. The inhibitory effects of candesartan on responses to angiotensin II were long in duration, and the AT1 receptor antagonist had little effect on baseline pressures. Candesartan was without effect on vasoconstrictor responses to norepinephrine, U46619, PGF2 alpha , and BAY K8644; on biphasic responses to endothelin-1; and on vasodilator responses to acetylcholine. Candesartan significantly attenuated hindquarters vasoconstrictor responses to angiotensin III and IV with a parallel shift at the 3 µg/kg iv dose and a nonparallel shift to the right at the high dose of the AT1 receptor antagonist. The results of the present study indicate that candesartan is a potent angiotensin AT1 receptor antagonist that can induce both competitive and noncompetitive blockade of responses to angiotensin II, III, and IV in the hindquarters vascular bed of the cat.Key words: angiotensin, vasoconstrictor responses, angiotensin type 1 receptors, selective and competitive antagonist, U46619.

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