The role of angiotensin receptor-1 blockade on electromechanical changes induced by left ventricular hypertrophy and its regression

Gray, Rosaire; Turner, Mark A.; Sheridan, Desmond J.; Fry, Christopher

doi:10.1016/j.cardiores.2006.11.017

Cited by 3 publications

(5 citation statements)

References 39 publications

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“…[21][22][23] The study from Yang et al 23 showed a significant reduction of 13% in LVM at day 1 after debanding and subsequent further reduction in LVM, but only in male mice. They identified a typical gene expression profile that was responsible for the fast regression.…”

Section: S26mentioning

confidence: 98%

Regression of Myocardial Hypertrophy After Aortic Valve Replacement

Petrov

Regitz‐Zagrosek²,

Lehmkuhl³

et al. 2010

Circulation

211

147

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Background-In patients with aortic stenosis, pressure overload induces cardiac hypertrophy and fibrosis. Female sex and estrogens influence cardiac remodeling and fibrosis in animal models and in men. Sex differences and their molecular mechanisms in hypertrophy regression after aortic valve replacement have not yet been studied. Methods and Results-We prospectively obtained preoperative and early postoperative echocardiography in 92 patients, 53 women and 39 men, undergoing aortic valve replacement for isolated aortic stenosis. We analyzed in a subgroup of 10 patients matrix gene expression in left ventricular (LV) biopsies. In addition, we determined the effect of 17␤-estradiol on collagen synthesis in isolated rat cardiac fibroblasts. Preoperatively, women and men had similar ejection fraction. Similar percentages of women and men had increased LV diameters (37% and 38%). Women more frequently exhibited LV hypertrophy than men (women: 86%; men: 56%; PϽ0.01). Postoperatively, increased LV diameters persisted in 34% of men but only in 12% of women (PϽ0.023). LV hypertrophy reversed more frequently in women than in men, leading to a similar prevalence of LV hypertrophy after surgery (women: 45%; men: 36%). In surgical biopsies, men had significantly higher collagen I and III and matrix metalloproteinase 2 gene expression than women. In isolated rat cardiac fibroblasts, 17␤-estradiol significantly increased collagen I and III gene expressions in male cells but decreased it in female cells. Conclusion-Women

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Section: S26mentioning

confidence: 98%

Regression of Myocardial Hypertrophy After Aortic Valve Replacement

Petrov

Regitz‐Zagrosek²,

Lehmkuhl³

et al. 2010

Circulation

211

147

View full text Add to dashboard Cite

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“…We therefore used techniques to measure directly CV and R j in a set of complimentary studies to test the hypothesis that in intact myocardium CV is a function of R j over a continuous range of values commensurate with moderate, naturally occurring ranges of coupling and uncoupling in pathological conditions. We used validated methods, 5,14 to measure R j and CV and their general relationship in guinea-pig myocardium from different cardiac chambers with and without a GJ blocker, carbenoxolone, and in human ventricular myocardium excised from patients with hypertrophic cardiomyopathy. We also examined the effects of carbenoxolone on local, submillimeter propagation in intact human myocardial propagation as inferred from changes in bipolar electrogram duration during clinical electrophysiology studies to determine how the ex vivo findings are manifest in, and may therefore be inferred from, clinical measurements.…”

Section: Clinical Perspective On P 1214mentioning

confidence: 99%

“…Methods have been described previously in detail 14 ; preparations were superfused with Tyrode solution (37°C, 4 mL·min −1 ) in a horizontal trough. Longitudinal CV was measured by stimulating the preparation at 1 end with insulated Ag-AgCl electrodes (10 µs pulses, 1 Hz, 1.5× threshold).…”

Section: Intracellular Electrophysiological Measurements and Measuremmentioning

confidence: 99%

Relationship Between Gap-Junctional Conductance and Conduction Velocity in Mammalian Myocardium

Dhillon

Gray

Kojodjojo

et al. 2013

Circ: Arrhythmia and Electrophysiology

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Background-Gap junction resistivity, R j , has been proposed as a key determinant of conduction velocity (CV). However, studies in connexin-gene knockout mice demonstrated significant CV slowing only with near-complete connexin deletion, and these findings led to the concept of a significant redundancy of myocardial gap junctions. We challenged this prevailing concept and addressed the hypothesis that there is a continuous relationship between R j and CV, each independently measured in human and guinea-pig myocardium. Methods and Results-R j and CV were directly measured by oil-gap impedance and microelectrode techniques in human left ventricular myocardium from patients with hypertrophic cardiomyopathy and in guinea-pig atrial and ventricular myocardium before and during pharmacological uncoupling with 20-µmol/L carbenoxolone. There was a continuous relationship between R j and CV in human and guinea-pig myocardium, pre-and post-carbenoxolone (r 2 =0.946; P<0.01). In guinea-pig left ventricle, left atrium, and right atrium, carbenoxolone increased R j by 28±9%, 26±16%, and 25±14% and slowed CV by 17±3%, 23±8%, and 11±4% respectively (all P<0.05 versus control). As a clinically accessible measure of local microscopic myocardial conduction slowing in vivo in the intact human heart, carbenoxolone prolonged electrogram duration in the right atrium (39.7±4.2 to 42.3±4.3 ms; P=0.01) and right ventricle (48.1±2.5 to 53.3±5.3 ms; P<0.01). Conclusions-There is a continuous relationship between R j and CV that is consistent between cardiac chambers and across species, indicating that naturally occurring variations in cellular coupling can account for variations in CV, and that the concept that there is massive redundancy of coupling is not tenable. (Circ Arrhythm Electrophysiol. 2013;6:1208-1214.)

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“…It has been shown previously when using thin trabeculae, as used for G j measurement, and bipolar stimulation at one end that there is one-dimensional (1-D) AP conduction along the longitudinal axis [18]. Under these specific conditions, AP conduction is described accurately by 1-D cable theory where G j is proportional to the square root on CV [7, 16].…”

Section: Resultsmentioning

confidence: 99%

“…Preparations were electrically stimulated with 50–100 μs pulses via Ag/AgCl bipolar electrodes on one end of the preparation [18]. Stimulating conditions were 1, 2 or 5 Hz in Tyrode’s solution and 1 Hz in low-Na solution.…”

Section: Methodsmentioning

confidence: 99%

Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction

Jabr

Hatch

Salvage

et al. 2016

Pflugers Arch - Eur J Physiol

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Cardiac arrhythmias are associated with raised intracellular [Ca2+] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca2+-dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca2+-dependent phosphatase, calcineurin. Intracellular [Ca2+] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca2 +]i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca2+]i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca2+-independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca2+]i. PP2A had no role. Conduction velocity was reduced by raised [Ca2+]i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca2+] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.Electronic supplementary materialThe online version of this article (doi:10.1007/s00424-016-1885-7) contains supplementary material, which is available to authorized users.

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The role of angiotensin receptor-1 blockade on electromechanical changes induced by left ventricular hypertrophy and its regression

Abstract: The electromechanical changes to hypertrophied myocardium are different in these two models of LVH. Moreover, losartan was ineffective in modulating the consequences of hypertrophy induced by constriction of the thoracic aorta.

Cited by 3 publications

References 39 publications

Regression of Myocardial Hypertrophy After Aortic Valve Replacement

Regression of Myocardial Hypertrophy After Aortic Valve Replacement

Relationship Between Gap-Junctional Conductance and Conduction Velocity in Mammalian Myocardium

Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction

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