Chronic angiotensin II stimulation in the heart produces an acquired long QT syndrome associated with IK1 potassium current downregulation

Domenighetti, Andrea A.; Boixel, Christophe; Céfaï, Daniel; Abriel, Hugues; Pedrazzini, Thierry

doi:10.1016/j.yjmcc.2006.09.019

Cited by 64 publications

(56 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is also well known that I K1 stabilizes the RMP and determines the cell input resistance, which is the resistance of the membrane in the subthreshold voltage range (33). Other researches have reported that I K1 is downregulated in several other cardiac disorders such as heart failure and long QT syndrome (34,35). The downregulation of I K1 is also observed in the models of cardiac hypertrophy and in the patients with cardiomyopathies (36).…”

Section: Discussionmentioning

confidence: 97%

Overexpression of M3 Muscarinic Receptor Is a Novel Strategy for Preventing Sudden Cardiac Death in Transgenic Mice

Liu¹,

Sun²,

Pan³

et al. 2011

Mol Med

View full text Add to dashboard Cite

The present study was designed to investigate the cardiac benefits of M 3 muscarinic receptor (M 3 -mAChR) overexpression and whether these effects are related to the regulation of the inward rectifying K + channel by microRNA-1 (miR-1) in a conditional overexpression mouse model. A cardiac-specific M 3 -mAChR transgenic mouse model was successfully established for the first time in this study using microinjection, and the overexpression was confirmed by both reverse transcriptase-polymerase chain reaction and Western blot techniques. We demonstrated that M 3 -mAChR overexpression dramatically reduced the incidence of arrhythmias and decreased the mortality in a mouse model of myocardial ischemia-reperfusion (I/R). By using whole-cell patch techniques, M 3 -mAChR overexpression significantly shortened the action potential duration and restored the membrane repolarization by increasing the inward rectifying K + current. By using Western blot techniques, M 3 -mAChR overexpression also rescued the expression of the inward rectifying K + channel subunit Kir2.1 after myocardial I/R injury. This result was accompanied by suppression of upregulation miR-1. We conclude that M 3 -mAChR overexpression reduced the incidence of arrhythmias and mortality after myocardial I/R by protecting the myocardium from ischemia in mice. This effect may be mediated by increasing the inward rectifying K + current by downregulation of arrhythmogenic miR-1 expression, which might partially be a novel strategy for antiarrhythmias, leading to sudden cardiac death.

show abstract

Section: Discussionmentioning

confidence: 97%

Overexpression of M3 Muscarinic Receptor Is a Novel Strategy for Preventing Sudden Cardiac Death in Transgenic Mice

Liu¹,

Sun²,

Pan³

et al. 2011

Mol Med

View full text Add to dashboard Cite

show abstract

“…The cellular mechanism(s) by which cilnidipine shortens the ventricular repolarization has not been fully elucidated at present. Previous in vitro electrophysiological studies have demonstrated that angiotensin II decreases IKr, transient outward K+ currents (Ito) and inward rectifier K+ currents (IK1) of the cardiomyocytes [27][28][29] and that aldosterone decreases Ito. [30] Based on the differences in the effects on the neurohumoral factors between cilnidipine and other drugs, it can be speculate that the inhibitory effect of cilnidipine on the renin-angiotensin-aldosterone system by its N-type calcium channel blocking action [31][32][33][34] may have decreased the suppression of the K+ channels.…”

Section: Discussionmentioning

confidence: 99%

Comparative assessment of effects of calcium channel antagonists, amlodipine, and cilnidipine, on QT interval in hypertensive patients - An observational study

Sarkar¹,

Srivastava²,

Mohanty³

2017

Natl J Physiol Pharm Pharmacol

View full text Add to dashboard Cite

Background:The duration of the QT interval as measured by 12-lead electrocardiography is a measure of myocardial repolarization and is widely used to describe cardiac abnormalities, to determine the presence of cardiac toxicity and to evaluate drug safety. In hypertension, the QT interval is a predictor of the risk of both coronary events and cardiovascular death, after adjusting for the effects of additional risk factors. According to AHA and JNC VIII calcium channel blockers are first-line drug in the treatment of hypertension. The equipotent antihypertensive effect of cilnidipine and amlodipine in their equivalent dose has been demonstrated in number of studies. Aims and Objectives: To compare and evaluate the effects of calcium channel antagonists amlodipine and cilnidipine on QT interval among hypertensive patients. Materials and Methods: A total of 258 patients were screened, examined, and enrolled as study participants during that period. The enrolled patients were then divided as (1) hypertensive patient (n = 159) -selected patients received either amlodipine (2.5-10 mg) or cilnidipine (5-20 mg) with or without angiotensin receptor blocker (ARB) and (2) hypertensive with controlled diabetic patients (n = 99) -selected patients received either amlodipine (2.5-10 mg) or cilnidipine (5-20 mg) with or without ARB along with antidiabetic medication. Calculated by Bazett's formula (most commonly used) = QT Interval/√ (relative risk [RR] interval) where RR interval = 60/heart rate, normal QTc ≤440 ms. The QT interval was measured at the baseline and after 12 months of treatment for hypertensive patients. Results: There was extremely significant QTc reduction was seen with cilnidipine therapy and significant elevation seen by amlodipine treatment but without any clinical relevance. While comparing the effect of amlodipine and cilnidipine, extremely significant as well as clinically relevant difference between the two treatments was noted. Conclusions: From this study, it can be concluded that cilnidipine reduces QTc interval, and hence is a better choice over amlodipine for patients suffering from long QT interval.

show abstract

“…20 The mechanisms of the repolarization prolongation have been related to angiotensin II and aldosterone. Angiotensin II inhibits potassium currents in cardiac myocytes both directly, through modulation of Kir2.1-Kir2.2 channel subunit expression and inward rectifier potassium (IK1) currents, 21 and indirectly, by increasing aldosterone production. Aldosterone has been shown to increase acutely action potential duration in humans.…”

Section: Discussionmentioning

confidence: 99%

Ventricular repolarization before and after treatment in patients with secondary hypertension due to renal-artery stenosis and primary aldosteronism

et al. 2011

View full text Add to dashboard Cite

A prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects. Patients with renal-artery stenosis and primary aldosteronism (PA) are at increased risk of cardiovascular events. The objective of the present study was to evaluate the QT interval in patients with renovascular hypertension (RV) and PA before and after treatment. A total of 24 patients with RV and 38 with PA were studied; 89 patients with essential hypertension (EH) served as control group. Corrected QT intervals (QTcH) were measured from a 12-lead ECG. Basal QTcH was longer in RV (429 ± 30 ms) and PA (423 ± 23 ms) compared with EH controls (407 ± 18 ms; Po0.001). The prevalence of QTcH 4440 ms was higher in RV (29%) and PA patients (29%) compared with EH controls (4%; Po0.001). QTcH interval was evaluated after treatment in 19 RV and 15 PA patients. QTcH was reduced after renal-artery angioplasty in RV patients (419±14 ms; P¼0.02), and after spironolactone or adrenalectomy in PA (403 ± 12 ms; P¼0.01). In conclusion, QT interval was prolonged in patients with RV and PA compared with controls with EH. After angioplasty of renal-artery stenosis in RV, and treatment with spironolactone or adrenalectomy in PA, the cardiovascular risk of such patients may be reduced by concomitant blood pressure lowering and QT duration shortening.

show abstract

Chronic angiotensin II stimulation in the heart produces an acquired long QT syndrome associated with IK1 potassium current downregulation

Cited by 64 publications

References 37 publications

Overexpression of M3 Muscarinic Receptor Is a Novel Strategy for Preventing Sudden Cardiac Death in Transgenic Mice

Overexpression of M3 Muscarinic Receptor Is a Novel Strategy for Preventing Sudden Cardiac Death in Transgenic Mice

Comparative assessment of effects of calcium channel antagonists, amlodipine, and cilnidipine, on QT interval in hypertensive patients - An observational study

Ventricular repolarization before and after treatment in patients with secondary hypertension due to renal-artery stenosis and primary aldosteronism

Contact Info

Product

Resources

About