Endothelin and angiotensin II stimulation of Na+-H+ exchange is impaired in cardiac hypertrophy.

Ito, Nobuhiko; Kagaya, Yutaka; Weinberg, Ellen O.; Barry, William H.; Lorell, Beverly H.

doi:10.1172/jci119123

Cited by 84 publications

(42 citation statements)

References 41 publications

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“…However, several studies reported that ET-1 showed a reduced or absent PIE in myocardium or isolated myocytes from diseased hearts (15,25,29,31,42,47). Similarly, Pieske et al (31) demonstrated that ET A -mediated PIE is attenuated in end-stage failing human ventricular muscle strips desspite an increase in ET A expression.…”

Section: Discussionmentioning

confidence: 99%

Contractile regulation by overexpressed ET_Arequires intact T tubules in adult rat ventricular myocytes

Chung

Kang²,

Walker³

2008

American Journal of Physiology-Heart and Circulatory Physiology

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Chung KY, Kang M, Walker JW. Contractile regulation by overexpressed ETA requires intact T tubules in adult rat ventricular myocytes. Am J Physiol Heart Circ Physiol 294: H2391-H2399, 2008. First published March 7, 2008 doi:10.1152/ajpheart.00011.2008.-Endothelin (ET)-1 regulates the contractility and growth of the heart by binding G protein-coupled receptors of the ET type A receptor (ETA)/ET type B (ETB) receptor family. ETA, the predominant ET-1 receptor subtype in myocardium, is thought to localize preferentially within cardiac T tubules, but the consequences of mislocalization are not fully understood. Here we examined the effects of the overexpression of ETA in conjunction with T-tubule loss in cultured adult rat ventricular myocytes. In adult myocytes cultured for 3 to 4 days, the normally robust positive inotropic effect (PIE) of ET-1 was lost in parallel with T-tubule degeneration and a decline in ETA protein levels. In these T tubule-compromised myocytes, an overexpression of ETA using an adenoviral vector did not rescue the responsiveness to ET-1, despite the robust expression in the surface sarcolemma. The inclusion of the actin polymerization inhibitor cytochalasin D (CD) during culture prevented gross morphological changes including a loss of T tubules and a rounding of intercalated discs, but CD alone did not rescue the responsiveness to ET-1 or prevent ETA downregulation. The rescue of a normal PIE in 3-to 4-day cultured myocytes required both an increased expression of ETA and intact T tubules (preserved with CD). Therefore, the activation of ETA localized in T tubules was associated with a strong PIE, whereas the activation of ET A in surface sarcolemma was not. The results provide insight into the pathological cardiac conditions in which ET A is upregulated and T-tubule morphology is altered. cytochalasin D; inotropism; endothelin type A receptor; heart failure THE POTENT vasoconstrictor peptide endothelin (ET)-1 is produced not only by vascular endothelial cells (46) but also by endocardial endothelial cells and cardiac myocytes (14). In the heart, ET-1 produces inotropic, chronotropic, and growthpromoting actions (30,38). Among these physiological effects of ET-1, the regulation of contractility has received considerable attention, with a positive inotropic effect (PIE) reported in rat, mouse, rabbit, ferret, and human but not in guinea pig or dog myocardium (18,22,(43)(44)(45). Biological functions of ET-1 are mediated by two G protein-coupled receptor (GPCR) subtypes, ET type A receptor (ET A ) and ET type B receptor

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Section: Discussionmentioning

confidence: 99%

Contractile regulation by overexpressed ET_Arequires intact T tubules in adult rat ventricular myocytes

Chung

Kang²,

Walker³

2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…A decrease in Na ϩ /H ϩ exchanger activity of cardiac papillary muscle has been reported in streptozotocin-induced diabetic rats (27). A defect in the coupling of PKC signaling with the Na ϩ /H ϩ exchanger has been shown in adult hypertrophied myocardium generated by aortic banding (28). Since PKC␤2 activation was observed in diabetic cardiomyopathy (29), and PKC␤2 overexpression mice had left ventricular hypertrophy (7), we cannot exclude the possibility that regulation of intracellular pH might be impaired in these mice and contribute to diminished cardiomyocyte function.…”

Section: Discussionmentioning

confidence: 99%

In vivo phosphorylation of cardiac troponin I by protein kinase Cbeta2 decreases cardiomyocyte calcium responsiveness and contractility in transgenic mouse hearts.

Takeishi¹,

Chu²,

Kirkpatrick³

et al. 1998

J. Clin. Invest.

173

108

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Recently, it has been reported that the protein kinase C (PKC) ␤ isoform plays a critical role in the development of hypertrophy and heart failure. The purpose of the present study was to clarify the mechanism by which activation of PKC ␤ led to depressed cardiac function. Thus, we used a PKC ␤ 2 overexpressing mouse, an animal model of heart failure, to examine mechanical properties and Ca 2 ϩ signals of isolated left ventricular cardiomyocytes. The percentage of shortening, rate of shortening, and rate of relengthening of cardiomyocytes were markedly reduced in PKC ␤ 2 overexpression mice compared to wild-type control mice, although the baseline level and amplitude of Ca 2 ϩ signals were similar. These findings suggested a decreased myofilament responsiveness to Ca 2 ϩ in transgenic hearts. Therefore, the incorporation of

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“…6,9,10 At 9 to 11 weeks after the surgery, after closed-chest LV pressure was recorded, the animals were euthanized and LV myocytes were prepared with collagenase perfusion by a method described previously. [11][12][13][14] Myocyte [Ca 2ϩ ] i was measured with fluo 3 (Molecular Probes, Inc) with an excitation wave length of 480Ϯ20 nm and emission signal detected at 535Ϯ25 nm. The optical system and calibration method for [Ca 2ϩ ] i are described in detail elsewhere.…”

Section: Methodsmentioning

confidence: 99%

“…[11][12][13][14] The pH i was measured with seminaphthorhodafluor-1 (SNARF 1-AM) (Molecular Probes, Inc) with an excitation wave length of 540 nm and emission signal detected at 580 and 640 nm. 12,13 The pH i for each cell was calibrated in situ by exposing cells to solutions of varying pH and was calculated by the method previously described. 12,13 At baseline, myocytes were superfused with oxygenated HEPESbuffered Tyrode's solution.…”

Section: Methodsmentioning

confidence: 99%

Atrial Natriuretic Peptide Has Different Effects on Contractility and Intracellular pH in Normal and Hypertrophied Myocytes From Pressure-Overloaded Hearts

Tajima¹,

Bartúnek²,

Weinberg³

et al. 1998

Circulation

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Background-Atrial natriuretic peptide (ANP) depresses contractility in left ventricular myocytes. Its expression is upregulated in pressure-overloaded hypertrophied hearts; however, the effects of ANP on contractility in hypertrophied myocytes are not known. Our aims were (1) to examine the cellular mechanisms of this depression in contractility in normal myocytes and (2) to test the hypothesis that the effects of ANP on contractility differ in hypertrophied myocytes from rats with ascending aortic stenosis. Methods and Results-We measured the myocyte shortening as an index of contractility, [Ca 2ϩ ] i with fluo 3, and pH i with seminaphthorhodafluor-1 (SNARF-1). In normal control myocytes (nϭ26), ANP caused a concentration-dependent depression of contractility and reduction in pH i . In the presence of 10 Ϫ6 mol/L ANP, fractional cell shortening was 78Ϯ5% of baseline (PϽ0.05) and pH i was reduced by 0.16Ϯ0.04 U from baseline (PϽ0.01) without changes in [Ca 2ϩ ] i . The magnitude of the depression of contraction caused by ANP was similar to that caused by intracellular acidification induced by an NH 4 Cl pulse. The effects of ANP on contractility and pH i were prevented in the presence of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), which inhibits the Na ϩ /H ϩ exchanger. In hypertrophied myocytes (nϭ23), ANP did not depress either myocyte contractility or pH i at concentrations of either 10 Ϫ8 , 10 Ϫ7 , or 10 Ϫ6 mol/L. ANP caused no change in pH i or the [Ca 2ϩ ] i transient in hypertrophied myocytes. The cGMP level was increased and Na ϩ /H

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Endothelin and angiotensin II stimulation of Na+-H+ exchange is impaired in cardiac hypertrophy.

Abstract: We compared the effects of endothelin-1 (ET-1) on intracellular pH, intracellular [

Cited by 84 publications

References 41 publications

Contractile regulation by overexpressed ET_Arequires intact T tubules in adult rat ventricular myocytes

Contractile regulation by overexpressed ET_Arequires intact T tubules in adult rat ventricular myocytes

In vivo phosphorylation of cardiac troponin I by protein kinase Cbeta2 decreases cardiomyocyte calcium responsiveness and contractility in transgenic mouse hearts.

Atrial Natriuretic Peptide Has Different Effects on Contractility and Intracellular pH in Normal and Hypertrophied Myocytes From Pressure-Overloaded Hearts

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Endothelin and angiotensin II stimulation of Na+-H+ exchange is impaired in cardiac hypertrophy.

Abstract: We compared the effects of endothelin-1 (ET-1) on intracellular pH, intracellular [

Cited by 84 publications

References 41 publications

Contractile regulation by overexpressed ETArequires intact T tubules in adult rat ventricular myocytes

Contractile regulation by overexpressed ETArequires intact T tubules in adult rat ventricular myocytes

In vivo phosphorylation of cardiac troponin I by protein kinase Cbeta2 decreases cardiomyocyte calcium responsiveness and contractility in transgenic mouse hearts.

Atrial Natriuretic Peptide Has Different Effects on Contractility and Intracellular pH in Normal and Hypertrophied Myocytes From Pressure-Overloaded Hearts

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Contractile regulation by overexpressed ET_Arequires intact T tubules in adult rat ventricular myocytes

Contractile regulation by overexpressed ET_Arequires intact T tubules in adult rat ventricular myocytes