scholarly journals Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components

2011 ◽  
Vol 43 (13) ◽  
pp. 829-835 ◽  
Author(s):  
Shea Gilliam-Davis ◽  
Patricia E. Gallagher ◽  
Valerie S. Payne ◽  
Sherry O. Kasper ◽  
Ellen N. Tommasi ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Receptor Mrna ◽  
Mas Receptor ◽  
Age Related ◽  
Old Rats ◽  
F344 Rats

In Fischer 344 (F344) rats, renin-angiotensin system (RAS) blockade for 1 yr with the angiotensin II type 1 (AT1) receptor blocker L-158,809 prevents age-related impairments in metabolic function, similar to transgenic rats with low glial angiotensinogen (Aogen). Brain RAS regulation may contribute to the benefits of long-term systemic AT1 antagonism. We assessed the mRNA of RAS components in the dorsomedial medulla of F344 rats at 3 (young; n = 8) or 15 mo of age (old; n = 7) and in rats treated from 3 to 15 mo of age with 20 mg/l of the AT1 receptor antagonist L-158,809 (Old+L; n = 6). Aogen and renin mRNA were lower in the young compared with old group. Angiotensin-converting enzyme (ACE) mRNA was lower in the old and Old+L compared with the young group. ACE2 and neprilysin expression were significantly higher in Old+L compared with young or old rats. AT1b, AT2, and Mas receptor mRNA were higher with treatment. Leptin receptor mRNA was lower in the old rats and this was prevented by L-158,809 treatment. Dual-specificity phosphatase 1 (DUSP1) mRNA was highest in the Old+L group. Aggregate correlate summation revealed a positive relationship for Mas receptor mRNA with food intake. The findings provide evidence for regulation of dorsomedial medullary renin and Aogen mRNA during aging. Long-term AT1 receptor blockade increases the mRNA of the enzymes ACE2 and neprilysin and the MAS receptor, which could potentially shift the balance from ANG II to ANG-(1–7) and prevent age-related declines in the leptin receptor and its signaling pathway.

scholarly journals Renin-Angiotensin System Inhibitor Usage and Age-Related Macular Degeneration among Hypertensive Patients: Results from the National Health and Nutrition Examination Survey, 2005–2008

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Chi Ren ◽  
Weiming Liu ◽  
Xue Yin ◽  
Bingyu Zhang ◽  
Peirong Lu
Keyword(s):  
Macular Degeneration ◽  
Treatment Duration ◽  
Renin Angiotensin System ◽  
Age Related Macular Degeneration ◽  
Nutrition Examination Survey ◽  
Angiotensin System ◽  
Hypertensive Patients ◽  
Health And Nutrition ◽  
Age Related

Purpose. To assess whether renin-angiotensin system inhibitor (RASI) utilization is associated with age-related macular degeneration (AMD) prevalence among hypertensive patients. Methods. A US population-based, cross-sectional study was conducted. 3,023 hypertensive participants aged 40 years and older with gradable retinal images and ascertained RASI usage in the National Health and Nutrition Examination Survey (NHANES), 2005–2008, were finally enrolled into the study. RASI usage was obtained by interview, and AMD was determined through retinal image assessment. We performed multivariable analyses to assess the relationship between utilization of RASIs and AMD prevalence. We also took drug treatment duration into account, in order to better understand the effects of RASIs. Results. Multivariable logistic regression analyses revealed that AMD prevalence had no significant association with RASI usage but was inversely correlated with RASI treatment duration (odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.78–0.98, p=0.02). Long-term usage (>5 years) of RASIs was significantly associated with not only reduced overall risk of AMD (OR = 0.23, 95% CI = 0.14–0.38, p<0.001) but also lower propensity to have early (OR = 0.23, 95% CI = 0.14–0.37, p<0.001) and late (OR = 0.25, 95% CI = 0.07–0.87, p=0.03) AMD. Furthermore, long-term RASI users were less prone to develop soft drusen (OR = 0.67, 95% CI = 0.45–0.99, p=0.04) and geographic atrophy (GA) (OR = 0.39, 95% CI = 0.22–0.71, p=0.003). Conclusions. Evidence supporting that RASI utilization could directly protect against AMD in hypertensive patients was still insufficient, but long-term RASI treatment seemed to be beneficial for both early and late AMD, implicating a promising therapeutic approach that RASIs might offer for AMD prevention and management.

scholarly journals Covid-19: the renin–angiotensin system imbalance hypothesis

2020 ◽  
Vol 134 (11) ◽  
pp. 1259-1264 ◽  
Author(s):  
Katharina Lanza ◽  
Lucas G. Perez ◽  
Larissa B. Costa ◽  
Thiago M. Cordeiro ◽  
Vitria A. Palmeira ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Renin Angiotensin System ◽  
Disease Course ◽  
Ang Ii ◽  
Cellular Mechanisms ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Mas Receptor

Abstract The emergency of SARS-CoV-2 in China started a novel challenge to the scientific community. As the virus turns pandemic, scientists try to map the cellular mechanisms and pathways of SARS-CoV-2 related to the pathogenesis of Coronavirus Disease 2019 (Covid-19). After transmembrane angiotensin-converting enzyme 2 (ACE2) has been found to be SARS-CoV-2 receptor, we hypothesized an immune-hematological mechanism for Covid-19 based on renin–angiotensin system (RAS) imbalance to explain clinical, laboratory and imaging findings on disease course. We believe that exaggerated activation of ACE/Angiotensin II (Ang II)/Angiotensin Type 1 (AT1) receptor RAS axis in line with reduction of ACE2/Angiotensin-(1-7)/Mas receptor may exert a pivotal role in the pathogenesis of Covid-19. In this perspective, we discuss potential mechanisms and evidence on this hypothesis.

Epochs in the depressor/pressor balance of the renin–angiotensin system

2016 ◽  
Vol 130 (10) ◽  
pp. 761-771 ◽  
Author(s):  
Katrina M. Mirabito Colafella ◽  
Lucinda M. Hilliard ◽  
Kate M. Denton
Keyword(s):  
Extracellular Fluid ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Mas Receptor ◽  
Angiotensin Type 2 Receptor ◽  
Angiotensin Type

The renin–angiotensin system (RAS) plays a commanding role in the regulation of extracellular fluid homoeostasis. Tigerstadt and Bergman first identified the RAS more than two centuries ago. By the 1980s a voyage of research and discovery into the mechanisms and actions of this system led to the development of drugs that block the RAS, which have become the mainstay for the treatment of cardiovascular and renal disease. In the last 25 years new components of the RAS have come to light, including the angiotensin type 2 receptor (AT2R) and the angiotensin-converting enzyme 2 (ACE2)/angiotensin-(1–7) [Ang(1–7)]/Mas receptor (MasR) axis. These have been shown to counter the classical actions of angiotensin II (AngII) at the predominant angiotensin type 1 receptor (AT1R). Our studies, and those of others, have demonstrated that targeting these depressor RAS pathways may be therapeutically beneficial. It is apparent that the evolution of both the pressor and depressor RAS pathways is distinct throughout life and that the depressor/pressor balance of the RAS vary between the sexes. These temporal patterns of expression suggest that therapies targeting the RAS could be optimized for discrete epochs in life.

scholarly journals Placental insufficiency results in temporal alterations in the renin angiotensin system in male hypertensive growth restricted offspring

2007 ◽  
Vol 293 (2) ◽  
pp. R804-R811 ◽  
Author(s):  
Daniela Grigore ◽  
Norma B. Ojeda ◽  
Elliot B. Robertson ◽  
Antoinette S. Dawson ◽  
Contrina A. Huffman ◽  
...  
Keyword(s):  
Regulatory System ◽  
Renin Angiotensin System ◽  
Ace Inhibition ◽  
Placental Insufficiency ◽  
Late Gestation ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Uterine Perfusion

Reduced uterine perfusion initiated in late gestation in the rat results in intrauterine growth restriction (IUGR) and development of hypertension by 4 wk of age. We hypothesize that the renin angiotensin system (RAS), a regulatory system important in the long-term control of blood pressure, may be programmed by placental insufficiency and may contribute to the etiology of IUGR hypertension. We previously reported that RAS blockade abolished hypertension in adult IUGR offspring; however, the mechanisms responsible for the early phase of hypertension are unresolved. Therefore, the purpose of this study was to examine RAS involvement in early programmed hypertension and to determine whether temporal changes in RAS expression are observed in IUGR offspring. Renal renin and angiotensinogen mRNA expression were significantly decreased at birth (80 and 60%, respectively); plasma and renal RAS did not differ in conjunction with hypertension (mean increase of 14 mmHg) in young IUGR offspring; however, hypertension (mean increase of 22 mmHg) in adult IUGR offspring was associated with marked increases in renal angiotensin-converting enzyme (ACE) activity (122%) and renal renin and angiotensinogen mRNA (7-fold and 7.4-fold, respectively), but no change in renal ANG II or angiotensin type 1 receptor. ACE inhibition (enalapril, 10 mg·kg−1·day−1, administered from 2 to 4 wk of age) abolished hypertension in IUGR at 4 wk of age (decrease of 15 mmHg, respectively) with no significant depressor effect in control offspring. Therefore, temporal alterations in renal RAS are observed in IUGR offspring and may play a key role in the etiology of IUGR hypertension.

scholarly journals Long-term hemodynamic and molecular effects persist after discontinued renin–angiotensin system blockade in patients with type 1 diabetes mellitus

2013 ◽  
Vol 84 (6) ◽  
pp. 1246-1253 ◽  
Author(s):  
David Z.I. Cherney ◽  
Bernard Zinman ◽  
Christopher R.J. Kennedy ◽  
Rahim Moineddin ◽  
Vesta Lai ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Molecular Effects

scholarly journals Sex-related differences in the intratubular renin-angiotensin system in two-kidney, one-clip hypertensive rats

2019 ◽  
Vol 317 (3) ◽  
pp. F670-F682 ◽  
Author(s):  
Sang Ho Lee ◽  
Yu Ho Lee ◽  
Su Woong Jung ◽  
Dong Jin Kim ◽  
Seon Hwa Park ◽  
...  
Keyword(s):  
Renal Artery ◽  
Renin Angiotensin System ◽  
Female Rats ◽  
Male Rats ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor

The intratubular renin-angiotensin system (RAS) is thought to play an essential role in hypertensive renal disease, but information regarding sex-related differences in this system is limited. The present study investigated sex differences in the intratubular RAS in two-kidney, one-clip (2K1C) rats. A 2.5-mm clip was placed on the left renal artery of Sprague-Dawley rats, and rats were euthanized 3 or 5 wk after the operation. Systolic blood pressure increased in 2K1C rats in both sexes but was significantly higher in male rats than in female rats, and an antihypertensive effect was not observed in 2K1C ovariectomized (OVX) female rats. Compared with male 2K1C rats, intratubular angiotensin-converting enzyme (ACE) and ANG II were repressed, and intratubular ACE2, angiotensin (1–7), and Mas receptor were increased in both kidneys in female 2K1C rats 5 wk after surgery. Comparison with male and female rats and intratubular mRNA levels of ACE and ANG II type 1 receptor were augmented in OVX female rats, regardless of the clipping surgery 3 wk postoperation. ANG II type 2 receptor was upregulated in female rats with or without OVX; thus, the ANG II type 1-to-type 2 receptor ratio was higher in male rats than in female rats. In conclusion, female rats were protected from hypertensive renal and cardiac injury after renal artery clipping. An increase in the intratubular nonclassic RAS [ACE2/angiotensin (1–7)/Mas receptor] and a decrease in the ANG II type 1-to-type 2 receptor ratio could limit the adverse effects of the classic RAS during renovascular hypertension in female rats, and estrogen is suggested to play a primary role in the regulation of intratubular RAS components.

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.

Physical Exercise and ACE2-Angiotensin-(1-7)-Mas Receptor Axis of the Renin Angiotensin System

2017 ◽  
Vol 24 (9) ◽  
Author(s):  
Albena Nunes-Silva ◽  
Guilherme Carvalho Rocha ◽  
Daniel Massote Magalhaes ◽  
Lucas Neves Vaz ◽  
Marcelo Henrique Salviano de Faria ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor

UPREGULATION OF RENIN ANGIOTENSIN SYSTEM IN TYPE 1 DIABETES MELLITUS ASSOCIATED WITH HYPERTENSION

2011 ◽  
Vol 29 ◽  
pp. e377-e378
Author(s):  
L. Morais ◽  
I. Watanabe ◽  
M. Franco ◽  
D. Arita ◽  
M. Gabbay ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin
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