scholarly journals Irbesartan prevents sodium channel remodeling in a canine model of atrial fibrillation

2018 ◽  
Vol 19 (1) ◽  
pp. 147032031875526 ◽  
Author(s):  
Xuewen Wang ◽  
Guangping Li
Keyword(s):  
Atrial Fibrillation ◽  
Sodium Current ◽  
Renin Angiotensin System ◽  
Canine Model ◽  
Atrial Pacing ◽  
Chain Reaction ◽  
Patch Clamp Technique ◽  
Angiotensin System ◽  
Whole Cell Patch Clamp ◽  
Polymerase Chain

Introduction: Activation of the renin-angiotensin system (RAS) plays an important role in atrial electrical remodeling (AER). The purpose of the present study was to evaluate the effects of irbesartan on cardiac sodium current (INa) in a canine model of atrial fibrillation. Materials and methods: Eighteen dogs were randomized into sham, pacing or pacing+irbesartan groups ( n = 6 in each group). The dogs in the pacing and irbesartan group were paced at 500 bpm for two weeks. Irbesartan (60 mg·kg−1·d−1) was administered orally in the pacing+irbesartan groups. INa was recorded using the whole-cell patch clamp technique from canine atrial myocytes. The expressions of cardiac Na+ channels (Nav1.5) mRNA were semi-quantified by reverse transcription-polymerase chain reaction. Results: Our results showed that INa density and Nav1.5 mRNA expression in the pacing group decreased significantly ( p < 0.05 vs. sham). However, rapid atrial pacing had no effects on the half-activation voltage (V1/2act) and half-inactivation voltage (V1/2inact) of INa ( p > 0.05 vs. sham). Irbesartan significantly increased INa densities and gene expression and hyperpolarized V1/2act without concomitant changes in V1/2inact. Conclusions: Irbesartan significantly increased INa densities, which contributed to improving intra-atrial conduction and prevented the induction and promotion of AF in atrial pacing dogs.

scholarly journals Association of ACE DD Genotype with Hypertension among the Tribal Populations of South India

2016 ◽  
Vol 52 ◽  
pp. 1-8 ◽  
Author(s):  
Raghu Paramasivam ◽  
Nandhakumar Rengasamy ◽  
Deva Arumugam ◽  
Prabhakaran Krishnan
Keyword(s):  
South India ◽  
Renin Angiotensin System ◽  
Chain Reaction ◽  
Specific Primers ◽  
Angiotensin System ◽  
Allele Specific ◽  
Tribal Populations ◽  
Important Regulator ◽  
Polymerase Chain ◽  
Vasoactive Peptide

The Renin-Angiotensin System (RAS) is an important regulator of the blood pressure (BP). The level of the vasoactive peptide Angiotensin-II, is mainly determined by the RAS enzyme, angiotensin converting enzyme-1 (ACE-1). Polymorphisms in ACE gene is reported to be associated with hypertension in various populations worldwide. We investigated the association of ACE I/D polymorphisms with hypertension among the tribal populations of South India. Samples were collected from hypertensive patients (n = 33) and healthy controls (n = 37). Genotyping was performed using Polymerase chain reaction (PCR) with allele specific primers. The DD genotype is significantly observed among the cases (OR = 1.0). Specifically, the DD genotype is more evident among the females (OR = 0 .705) than males (OR = 1.22) and is analysed to be associated with hypertension among the tribal populations of South India.

Stretch-mediated activation of cardiac renin gene

1994 ◽  
Vol 267 (4) ◽  
pp. H1630-H1636 ◽  
Author(s):  
P. H. Boer ◽  
M. Ruzicka ◽  
W. Lear ◽  
E. Harmsen ◽  
J. Rosenthal ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Renin Angiotensin System ◽  
Volume Overload ◽  
Mrna Levels ◽  
Shunt Surgery ◽  
Chain Reaction ◽  
Angiotensin System ◽  
Renin Gene ◽  
Renin Mrna ◽  
Polymerase Chain

This study was designed to quantitate cardiac mRNA levels encoding components of the local renin-angiotensin system during the development of volume overload-induced cardiac hypertrophy. Changes in cardiac renin mRNA levels were measured in relation to renin activity in the left ventricle (LV) and in plasma after acute passive stretch of the heart caused by an aortovenocaval shunt in the rat. A quantitative reverse-transcriptase polymerase chain reaction method with competitive internal standards was used to measure mRNA levels in total RNA derived from cardiac tissues after shunt. Seven days after shunt surgery, LV weight was increased by 23%. Renin activities were elevated four- and twofold in plasma and LV, respectively. LV angiotensinogen mRNAs were not significantly increased by shunt surgery; they were twofold higher than phosphoglycerate kinase mRNA from the housekeeping gene PGK-1. By day 7, LV levels for renin mRNA were significantly increased from well below 0.25% to approximately 1% of PGK-1 mRNA. Identity between renin polymerase chain reaction products from kidney and heart cDNAs and absence of "reninlike" amplification products were supported by Southern blotting. Volume overload caused increased expression of the renin gene in the stretched myocardium. This finding is consistent with the concept of a myocardial renin-angiotensin system that can be activated by locally produced renin and contributes to the hypertrophy of cardiac muscle.

scholarly journals Intermittent Hypoxia Upregulates the Renin and Cd38 mRNAs in Renin-Producing Cells via the Downregulation of miR-203

2021 ◽  
Vol 22 (18) ◽  
pp. 10127
Author(s):  
Yoshinori Takeda ◽  
Asako Itaya-Hironaka ◽  
Akiyo Yamauchi ◽  
Mai Makino ◽  
Sumiyo Sakuramoto-Tsuchida ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Sleep Apnea Syndrome ◽  
Renin Angiotensin System ◽  
Negative Control ◽  
Target Sequence ◽  
Mrna Levels ◽  
Chain Reaction ◽  
Angiotensin System ◽  
Cyclic Adp Ribose ◽  
Polymerase Chain

Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), and it is a known risk factor for hypertension. The upregulation of the renin-angiotensin system has been reported in IH, and the correlation between renin and CD38 has been noted. We exposed human HEK293 and mouse As4.1 renal cells to experimental IH or normoxia for 24 h and then measured the mRNA levels using a real-time reverse transcription polymerase chain reaction. The mRNA levels of Renin (Ren) and Cd38 were significantly increased by IH, indicating that they could be involved in the CD38-cyclic ADP-ribose signaling pathway. We next investigated the promotor activities of both genes, which were not increased by IH. Yet, a target mRNA search of the microRNA (miRNA) revealed both mRNAs to have a potential target sequence for miR-203. The miR-203 level of the IH-treated cells was significantly decreased when compared with the normoxia-treated cells. The IH-induced upregulation of the genes was abolished by the introduction of the miR-203 mimic, but not the miR-203 mimic NC negative control. These results indicate that IH stress downregulates the miR-203 in renin-producing cells, thereby resulting in increased mRNA levels of Ren and Cd38, which leads to hypertension.

scholarly journals Analysis of the input of polymorphism of several candidate genes in the development of hypertension and myocardial remodeling: in the sample of sibling pairs

2011 ◽  
Vol 17 (5) ◽  
pp. 488-492
Author(s):  
N. R. Khasanov ◽  
V. N. Oslopov ◽  
P. A. Slominskiy
Keyword(s):  
Renin Angiotensin System ◽  
Myocardial Remodeling ◽  
Myocardial Mass ◽  
Chain Reaction ◽  
Angiotensin System ◽  
Hypertensive Patients ◽  
Sibling Pairs ◽  
Polymerase Chain ◽  
Design And Methods ◽  
Agt Gene

Objective. To assess the contribution of the renin-angiotensin system, lipid metabolism and gene regulators of apoptosis in the development of hypertension and myocardial remodeling using sibling-pair and associative methods. Design and methods. Myocardial mass and myocardial mass index were calculated by echocardiography method, gene polymorphism was identified by polymerase chain reaction. Results. We found the association of genotype M235M AGT gene with hypertension in representatives of the Tatar ethnic group. Genotype A603A gene EAAT2 is associated with higher systolic blood pressure, and genotype CC rs189994 AIF gene is related to the greater myocardial mass in hypertensive patients.

scholarly journals EVALUATION OF AN INTERRELATION OF TARGET BLOOD PRESSURE ACHIEVEMENT AND COMPLICATIONS AND OUTCOMES OF PREGNANCY IN ARTERIAL HYPERTENSION

2014 ◽  
Vol 13 (6) ◽  
pp. 23-27 ◽  
Author(s):  
V. S. Chulkov ◽  
N. K. Vereina ◽  
S. P. Sinitsyn ◽  
V. F. Dolgushina
Keyword(s):  
Arterial Hypertension ◽  
Pregnant Women ◽  
Clinical Course ◽  
Renin Angiotensin System ◽  
Standard Laboratory ◽  
Chain Reaction ◽  
Genetic Investigation ◽  
Angiotensin System ◽  
Lower Weight ◽  
Polymerase Chain

Aim. To evaluate the influence of target BP achievement on clinical course and outcomes of pregnancy in pregnant women with arterial hypertension (AH).Material and methods. A cohort study with prospective cohort. Totally 300 pregnant women included; of those in to the 1st group 103 included with AH, who had not reached target BP; into the 2nd – 97 women with AH, who had reached target BP; control consisted of 100 women without AH. Women underwent clinical examination and observation, analysis of medical data, standard laboratory and instrumental investigation, genetic investigation by polymerase chain reaction.Results. Women who had not reached target BP pregnancy complicated more often with fetus development retardation and pre-eclampsy, and in pregancy outcomes there were preterm delivery and antenatal fetus death, newborns from this group had lower weight and height; also they had more often mutation of D-allele of ACE gene (I/D) and mutant C-allele of receptor 1 type angiotensine II gene (ATR11166 A/C) comparing to the group with achieved BP and with controls. By the result of logistic regression study the factor independently associated with total worse outcome, were premature deliveries in anamnesis - increase the risk almost 6 times (OR=5,93, 95% CI 1,83-19,2; p=0,003), pre-eclampsy during current preganancy – increases risk 3,7 times (OR=3,68, 95% CI 1,48-9,16; p=0,005), and target BP acievement (less than 140/90 mmHg) decreases the risk of total negative outcome 8 times (OR=0,12, 95% CI 0,05-0,28; p<0,001).Conclusion. Target BP achievement in pregnant women with AH might be an independent factor influencing the prevalence of obstetric complications and negative outcomes of pregnancy. A definite impact on target BP levels achievement make genetic polymorphisms of renin-angiotensin system genes.

Acute effects of repetitive depolarization on sodium current in chick myocytes

1991 ◽  
Vol 260 (6) ◽  
pp. H1810-H1818
Author(s):  
M. R. Gold ◽  
G. R. Strichartz
Keyword(s):  
Time Course ◽  
Sodium Current ◽  
Complete Recovery ◽  
Acute Effects ◽  
Na Current ◽  
Patch Clamp Technique ◽  
Membrane Hyperpolarization ◽  
Atrial Cells ◽  
Whole Cell Patch Clamp ◽  
Recovery From Inactivation

Acute effects of repetitive depolarization on the inward Na+ current (INa) of cultured embryonic chick atrial cells were studied using the whole cell patch-clamp technique. Stimulation rates of 1 Hz or greater produced a progressive decrement of peak INa. With depolarizations to 0 mV of 150-ms duration, applied at 2 Hz from a holding potential of -100 mV, the steady-state decrement was approximately 20%. The magnitude of this effect increased with stimulation frequency and with test potential depolarization and decreased with membrane hyperpolarization. Analysis of INa kinetics revealed that reactivation was sufficiently slow to preclude complete recovery from inactivation with interpulse intervals less than 1,000 ms. Moreover, reactivation accelerated markedly with membrane hyperpolarization, in parallel with the response to repetitive stimulation. The multiexponential time course of recovery of peak INa from repetitive depolarization was similar to that observed after single stimuli; however, there was a shift toward a greater proportion of current recovering with the slower of two time constants. It is concluded that incomplete recovery from inactivation is responsible for the decrement in INa observed with short interpulse intervals.

scholarly journals Polymorphisms of the angiotensin-converting enzyme and angiotensinogen gene in patients with atrial fibrillation

2011 ◽  
Vol 12 (4) ◽  
pp. 549-556 ◽  
Author(s):  
Nurdan Papila Topal ◽  
Beste Ozben ◽  
Veysel Sabri Hancer ◽  
Azra Meryem Tanrikulu ◽  
Reyhan Diz-Kucukkaya ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Angiotensin Converting Enzyme ◽  
Left Atrium ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Ras Genes ◽  
Angiotensinogen Gene ◽  
M235t Polymorphism

Activation of the renin–angiotensin system (RAS) is associated with atrial fibrillation (AF). The aim of this study was to investigate the relation between AF and polymorphisms in RAS. One hundred and fifty patients with AF, 100 patients with no documented episode of AF and 100 healthy subjects were consecutively recruited into the study. The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and the M235T, A-20C, and G-6A polymorphisms of the angiotensinogen gene were genotyped. Patients with AF had significantly lower frequency of II genotype of ACE I/D and higher frequency of angiotensinogen M235T polymorphism T allele and TT genotype and G-6A polymorphism G allele and GG genotype compared with the controls. AF patients had significantly larger left atrium, higher left ventricular mass index (LVMI) and higher frequency of significant valvular pathology. ACE I/D polymorphism II genotype, angiotensinogen M235T polymorphism TT genotype and G allele and GG genotype of angiotensinogen G-6A polymorphism were still independently associated with AF when adjusted for left atrium, LVMI and presence of significant valvular pathology. Genetic predisposition might be underlying the prevalence of acquired AF. Patients with a specific genetic variation in the RAS genes may be more liable to develop AF.

scholarly journals Angiotensin-(1–7) increases neuronal potassium current via a nitric oxide-dependent mechanism

2011 ◽  
Vol 300 (1) ◽  
pp. C58-C64 ◽  
Author(s):  
Rui-Fang Yang ◽  
Jing-Xiang Yin ◽  
Yu-Long Li ◽  
Matthew C. Zimmerman ◽  
Harold D. Schultz
Keyword(s):  
Nitric Oxide ◽  
Neuronal Activity ◽  
Renin Angiotensin System ◽  
Protective Role ◽  
Patch Clamp Technique ◽  
Angiotensin System ◽  
The Central Nervous System ◽  
Nos Inhibitor ◽  
Inos Inhibition ◽  
Dependent Mechanism

Actions of angiotensin-(1–7) [Ang-(1–7)], a heptapeptide of the renin-angiotensin system, in the periphery are mediated, at least in part, by activation of nitric oxide (NO) synthase (NOS) and generation NO·. Studies of the central nervous system have shown that NO· acts as a sympathoinhibitory molecule and thus may play a protective role in neurocardiovascular diseases associated with sympathoexcitation, such as hypertension and heart failure. However, the contribution of NO in the intraneuronal signaling pathway of Ang-(1–7) and the subsequent modulation of neuronal activity remains unclear. Here, we tested the hypothesis that neuronal NOS (nNOS)-derived NO· mediates changes in neuronal activity following Ang-(1–7) stimulation. For these studies, we used differentiated catecholaminergic (CATH.a) neurons, which we show express the Ang-(1–7) receptor (Mas R) and nNOS. Stimulation of CATH.a neurons with Ang-(1–7) (100 nM) increased intracellular NO levels, as measured by 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM) fluorescence and confocal microscopy. This response was significantly attenuated in neurons pretreated with the Mas R antagonist (A-779), a nonspecific NOS inhibitor (nitro-l-arginine methyl ester), or an nNOS inhibitor ( S-methyl-l-thiocitrulline, SMTC), but not by endothelial NOS (eNOS) or inhibitory NOS (iNOS) inhibition {l- N-5-(1-iminoethyl)ornithine (l-NIO) and 1400W, respectively}. To examine the effect of Ang-(1–7)-NO· signaling on neuronal activity, we recorded voltage-gated outward K+ current ( IKv) in CATH.a neurons using the whole cell configuration of the patch-clamp technique. Ang-(1–7) significantly increased IKv, and this response was inhibited by A-779 or S-methyl-l-thiocitrulline, but not l-NIO or 1400W. These findings indicate that Ang-(1–7) is capable of increasing nNOS-derived NO· levels, which in turn, activates hyperpolarizing IKv in catecholaminergic neurons.

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