Hypertrophy alters effect of Ins(1,4,5)P3 on Ca2+ release in skinned rat heart muscle

1991 ◽  
Vol 260 (5) ◽  
pp. H1612-H1618 ◽  
Author(s):  
N. Furukawa ◽  
A. L. Bassett ◽  
T. Furukawa ◽  
R. J. Myerburg ◽  
S. Kimura
Keyword(s):  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Contractile Dysfunction ◽  
Body Weight Ratio ◽  
Rat Hearts ◽  
Inositol 1,4,5 Trisphosphate ◽  
Normal Rat ◽  
Skinned Cardiac Fibers

The effects of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] on the ability of the sarcoplasmic reticulum (SR) to accumulate and release Ca2+ and on the Ca2+ sensitivity of the contractile proteins were investigated using chemically (saponin) skinned cardiac fibers (60–120 microns diam) obtained from normal and pressure-overloaded hypertrophied rat left ventricles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta 3-6 wk before study. Age- and weight-matched normal rats served as controls. Pressure overload increased the left ventricular weight-to-body weight ratio by 45%. Ins(1,4,5)P3 at a concentration of 10 microM did not change the Ca(2+)-tension relationship at Ca2+ concentrations of 10(-7) to 10(-5) M in either normal or hypertrophied fibers. Ins(1,4,5)P3 also did not influence Ca2+ uptake by the SR in either normal or hypertrophied fibers. Ins(1,4,5)P3 did not induce Ca2+ release from the SR directly in either group. However, pretreatment with Ins(1,4,5)P3 enhanced the 5 mM caffeine-induced Ca2+ release by 80.5 +/- 22.7% in normal fibers enhances, rather than directly induces, SR Ca2+ release in normal rat hearts and that sustained pressure overload diminishes the response of the SR Ca(2+)-release system to Ins(1,4,5)P3, an action that may be partly responsible for contractile dysfunction in cardiac hypertrophy.

Effect of acidosis on contractile system in skinned fibers of hypertrophied rat heart

1990 ◽  
Vol 259 (4) ◽  
pp. H1044-H1049 ◽  
Author(s):  
S. Kimura ◽  
A. L. Bassett ◽  
T. Furukawa ◽  
N. Furukawa ◽  
R. J. Myerburg
Keyword(s):  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Contractile Dysfunction ◽  
Depressing Effect ◽  
Body Weight Ratio ◽  
Contractile System ◽  
The Right ◽  
Skinned Cardiac Fibers

Hypertrophied hearts have enhanced susceptibility to ischemia-induced contractile dysfunction. To explore the mechanisms of this phenomenon, we studied the effect of acidosis on the Ca2+ sensitivity of the contractile proteins and on Ca2+ accumulation by the sarcoplasmic reticulum (SR) in chemically (saponin) skinned cardiac fibers obtained from normal and pressure-overloaded hypertrophied rat left ventricles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta 6-8 wk before study. Age- and weight-matched normal rats served as controls. Pressure overload increased the left ventricular weight-to-body weight ratio by 48%. Reduction in pH shifted the pCa-tension curve to the right similarly in normal and hypertrophied preparations, and there was no difference in pCa-tension relationship at pH 7.0 or 6.5 between the two groups. However, reducing the pH of 1 microM Ca2(+)-loading solution from 7.0 to 6.5 decreased the amount of Ca2+ accumulated in the SR to 66.2 +/- 3.0% in normal fibers and 43.2 +/- 4.0% in hypertrophied fibers (P less than 0.01). We conclude that the enhanced susceptibility of hypertrophied hearts to ischemia-induced diastolic dysfunction may be partly explained by the greater depressing effect of acidosis on Ca2+ accumulation by the SR.

Sarcoplasmic reticulum function in skinned fibers of hypertrophied rat ventricle

1989 ◽  
Vol 256 (4) ◽  
pp. H1006-H1011 ◽  
Author(s):  
S. Kimura ◽  
A. L. Bassett ◽  
K. Saida ◽  
M. Shimizu ◽  
R. J. Myerburg
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Body Weight Ratio ◽  
Contractile System ◽  
Rat Ventricle ◽  
Skinned Cardiac Fibers ◽  
Contractile Performance

This study was designed to examine the Ca2+ sensitivity of the contractile system and the ability of the sarcoplasmic reticulum (SR) to accumulate and release Ca2+ in chemically (saponin) skinned cardiac fibers obtained from normal and pressure-overloaded hypertrophied rat left ventricles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta 6-8 wk before study. Age- and weight-matched normal rats served as controls. Pressure over-load increased the left ventricular weight-to-body weight ratio by 51%. There were no differences in the Ca2+-tension relationship between normal and hypertrophied preparations at Ca2+ concentrations of 10(-7) to 10(-4) M. Caffeine-induced Ca2+ release from the maximally Ca2+ -loaded SR was also not different between the two groups at caffeine concentrations of 0.5-30 mM. However, when the relative amount of Ca2+ accumulated in the SR with 10(-6), 3 x 10(-6), or 10(-5) M Ca2+ loading solutions for various loading periods was estimated by the area under the 25 mM caffeine-induced contraction, the accumulation of Ca2+ was significantly slower in hypertrophied fibers than in normal fibers. We conclude that depressed Ca2+ accumulation by the SR plays a role in modulation of contractile performance in this model of chronic pressure overload in rats.

Diminished effect of cAMP on Ca2+ accumulation in skinned fibers of hypertrophied rat heart

1994 ◽  
Vol 266 (2) ◽  
pp. H749-H756
Author(s):  
F. Tomita ◽  
A. L. Bassett ◽  
R. J. Myerburg ◽  
S. Kimura
Keyword(s):  
Body Weight ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Adrenergic Stimulation ◽  
Body Weight Ratio ◽  
The Right ◽  
Hypertrophied Ventricle ◽  
Concomitant Exposure

Sarcoplasmic reticulum (SR) Ca2+ uptake is reduced in the hypertrophied ventricle. To determine whether events initiated by beta-adrenergic stimulation are involved, we compared the effects of adenosine 3',5'-cyclic monophosphate (cAMP) on SR Ca2+ uptake between normal and pressure-overloaded hypertrophied hearts using saponin-skinned rat left ventricular muscles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta for 4–6 wk before study. Age-matched normal rats served as controls. Pressure overload increased the left ventricular weight-to-body weight ratio 60.8%. The SR was loaded by exposing the muscles to 10(-6) M Ca2+ solution; SR Ca2+ release was induced by 5 or 25 mM caffeine, and the amount of Ca2+ released from the SR was estimated by the area under the caffeine-induced transient contraction. Concomitant exposure to 10(-4) M cAMP did not influence caffeine-induced Ca2+ release in either normal or hypertrophied fibers. When 10(-4) M cAMP was applied during the Ca(2+)-loading periods, the amount of Ca2+ accumulated by the SR increased in both normal and hypertrophied fibers. However, the extent of increase was significantly smaller in hypertrophied fibers than in normal fibers [10.9 +/- 1.7 and 27.4 +/- 5.3% in 1 min of Ca2+ loading (P < 0.05), 12.2 +/- 3.2 and 24.7 +/- 3.8% in 4 min of Ca2+ loading (P < 0.05), respectively]. cAMP (10(-4) M) shifted the force-pCa relationship to the right similarly in normal and hypertrophied muscles, and there was no difference in the force-pCa relationship between the two groups either with or without cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Sarcoplasmic reticulum-related changes in cytosolic calcium in pressure-overload-induced feline LV hypertrophy

1993 ◽  
Vol 265 (6) ◽  
pp. H2009-H2016 ◽  
Author(s):  
B. A. Bailey ◽  
S. R. Houser
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Time Course ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Cytosolic Calcium ◽  
Left Ventricular ◽  
Heart Weight ◽  
Body Weight Ratio ◽  
Rest Periods ◽  
Premature Beats

Alterations in Ca2+ homeostasis that involve the sarcoplasmic reticulum (SR) were studied in feline left ventricular (LV) myocytes isolated from hearts with LV hypertrophy induced by slow, progressive pressure overload. At death, severe hypertrophy was evidenced by increased heart weight-to-body weight ratio (8.4 +/- 0.6 vs. 4.2 +/- 0.2 g/kg in controls). Steady-state Ca2+ transients (measured as. indo 1 fluorescence at 410 nm/480 nm; I410/I480) in LV hypertrophy (LVH) myocytes had diminished peak amplitudes (I410/I480 2.28 +/- 0.07 vs. 2.53 +/- 0.07 in controls) and prolonged durations (0.75 +/- 0.03 vs. 0.59 +/- 0.02 s in controls). The magnitude of shortening was reduced and the contractile duration was prolonged in LVH myocytes. The idea that changes in SR function are responsible for these alterations in the Ca2+ transient was tested by studying two aspects of SR-related Ca2+ homeostasis. Restitution of releasable SR Ca2+ was studied by measuring indo 1 transients and contractions during premature beats. The time course of restitution of both the indo 1 transient and contraction of hypertrophy myocytes was significantly slower than in controls. These data suggest that restitution of releasable SR Ca2+ is slowed in hypertrophy myocytes. The reduction of the indo 1 transient and contraction in beats following long rest periods (rest decay) was measured to determine the rate of Ca2+ loss from the SR. Rest decay was significantly (P < 0.05) more pronounced in hypertrophy myocytes, suggesting that Ca2+ loss from the SR is accelerated in these myocytes. (ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of cardiac overexpression of type 6 adenylyl cyclase affects on the response to chronic pressure overload

2010 ◽  
Vol 299 (3) ◽  
pp. H707-H712 ◽  
Author(s):  
Aziz Guellich ◽  
Shumin Gao ◽  
Chull Hong ◽  
Lin Yan ◽  
Thomas E. Wagner ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Contractile Function ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Body Weight Ratio ◽  
Aortic Constriction ◽  
Cross Sectional ◽  
Systolic Wall Stress

Adenylyl cyclase (AC) type 5 (AC5) and AC type 6 (AC6) are the two major AC isoforms in the heart. Cardiac overexpression of AC6 has been shown to be protective in response to several interventions. In this investigation, we examined the effects of chronic pressure overload in AC6 transgenic (TG) mice. In the absence of any stress, AC6 TG mice exhibited enhanced contractile function compared with their wild-type (WT) littermates, i.e., increased ( P < 0.05) left ventricular (LV) ejection fraction (EF) (75 ± 0.9 vs. 71 ± 0.5%) and LV dP/d t (7,850 ± 526 vs. 6,374 ± 315 mmHg/s). Forskolin (25 μg·kg−1·min−1 for 5 min) increased LVEF more ( P < 0.05) in AC6 TG mice (14.8 ± 1.0%) than in WT mice (7.7 ± 1.0%). Also, isoproterenol (0.04 μg·kg−1·min−1 for 5 min) increased LVEF more ( P < 0.05) in AC6 TG mice (18.0 ± 1.2%) than in WT mice (11.6 ± 2.1%). Pressure overload, induced by 4 wk of transverse aortic constriction (TAC), increased the LV weight-to-body weight ratio and myocyte cross-sectional area similarly in both groups, but reduced LVEF more in AC6 TG mice (22%) compared with WT mice (9%), despite the higher starting level of LVEF in AC6 TG mice. LV systolic wall stress increased more in AC6 TG mice than in WT mice, which could be responsible for the reduced LVEF in AC6 TG mice with chronic pressure overload. In addition, LV dP/d t was no longer elevated in AC6 TG mice after TAC compared with WT mice. LV end-diastolic diameter was also greater ( P < 0.05) in AC6 TG mice (3.8 ± 0.07 mm) than in WT mice (3.6 ± 0.05 mm) after TAC. Thus, in contrast to other interventions previously reported to be salutary with cardiac AC6 overpression, the response to chronic pressure overload was not; actually, AC6 TG mice fared worse than WT mice. The mechanism may be due to the increased LV systolic wall stress in AC6 TG mice with chronic pressure overload.

Abstract 1393: Inhibition of Cardiac Remodeling by Pravastatin is Associated with Amelioration of Endoplasmic Reticulum Stress

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hui Zhao ◽  
Yulin Liao ◽  
Tetsuo Minamino ◽  
Yoshihiro Asano ◽  
Masanori Asakura ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Er Stress ◽  
Cardiac Remodeling ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Stress Signaling ◽  
Body Weight Ratio ◽  
Stress Signaling Pathway

Background We previously reported that prolonged endoplasmic reticulum (ER) stress contributes to progression from cardiac hypertrophy to heart failure. Statins have an inhibitory effect on cholesterol synthesis, oxidative stresses, protein synthesis and production of inflammatory cytokines, all of which could be associated with ER stress. However, it is unknown whether statins can ameliorate ER stress in heart disease. This study was designed to investigate whether pravastatin could inhibit cardiac remodeling and ameliorate ER stress caused by pressure overload or tumor necrosis factor α (TNF α ). Methods and Results Cardiac hypertrophy was induced by transverse aortic constriction (TAC) for four weeks in C57BL/6 male mice. Either pravastatin (5 mg/kg/d, n=20, TAC+prava group) or its vehicle (n=20) was orally administered to mice. The ER stress signaling pathway was also studied in pressure-overloaded mice hearts and in cultured cardiomyocytes treated with TNF α (10ng/ml) for 24 hours. Four weeks after TAC, both heart-to-body weight ratio (8.68 ± 1.23 in TAC group, 6.92 ± 1.11 in TAC+prava group) and lung-to-body weight ratio (11.08 ± 2.58 in TAC group, 7.92± 3.56 in TAC+prava group) became significantly lower in pravastatin-treated mice than in the TAC group. Left ventricular fractional shortening and left ventricular ejection fraction (LVFS and LVEF) were larger in TAC+prava group (48.0±1.9 % and 80±1.9% respectively) compared with TAC group (LVFS and LVEF, 34.8 ±1.4% and 65 ±3%; P<0.01 VS TAC group each). Markers of ER stress such as an increase in ER chaperones and CHOP expressions and enhanced phosphorylation of eIF2 α were observed in the hearts of TAC mice, while pravastatin treatment significantly blunted these changes. Pravastatin-treated TAC mice also showed a decrease of cardiac apoptosis. Cardiac expression of TNF α was increased in TAC mice, and TNF α induced ER stress in cultured neonatal rat cardiomyocytes, either of which was significantly inhibited by pravastatin. Conclusions These findings indicate that pravastatin inhibits cardiac remodeling in mice subjected to pressure overload, and this action is associated with inhibition of the ER stress signaling pathway.

Ovariectomy augments pressure overload-induced hypertrophy associated with changes in Akt and nitric oxide synthase signaling pathways in female rats

2007 ◽  
Vol 293 (6) ◽  
pp. E1606-E1614 ◽  
Author(s):  
Md. Shenuarin Bhuiyan ◽  
Norifumi Shioda ◽  
Kohji Fukunaga
Keyword(s):  
Nitric Oxide ◽  
Body Weight ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Body Weight Ratio

To elucidate the molecular mechanism underlying estrogen-mediated cardioprotection in left ventricular (LV) hypertrophy and remodeling, we analyzed myocardial hypertrophy as well as cardiac function and hypertrophy-related protein expression in ovariectomized, aortic-banded rats. Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis. Effects on LV morphology and function were assessed using echocardiography, and expression of protein levels was determined by Western blot analysis. The heart-to-body weight ratio was most significantly increased in the OVX-pressure overload (PO) group compared with the OVX group and in the PO group compared with sham. The LV weight-to-body weight ratio was also significantly increased in the OVX-PO group compared with the OVX group and in the PO group compared with sham. The most significant increases in LV end diastolic pressure, LV developed pressure, and ±dp/d tmax were observed in the OVX-PO group compared with the OVX group and represent compensatory phenotypes against hypertrophy. Both endothelial nitric oxide (eNOS) synthase expression and activity was markedly reduced in the OVX-PO group, and protein kinase B (Akt) activity was largely attenuated. Marked breakdown of dystrophin was also seen in hearts of OVX-PO groups. Finally, significantly increased mortality was observed in the OVX-PO group following chronic isoproterenol administration. Our results demonstrate that rats subjected to ovariectomy are unable to compensate for hypertrophy, showed deteriorated heart function, and demonstrated increased mortality. Simultaneous impairment of eNOS and Akt activities and reduced dystrophin by ovariectomy likely contribute to cardiac decompensation during PO-induced hypertrophy in ovariectomized rats.

Downregulation of cyclin-dependent kinase inhibitors p21 and p27 in pressure-overload hypertrophy

1997 ◽  
Vol 273 (3) ◽  
pp. H1358-H1367 ◽  
Author(s):  
J. M. Li ◽  
G. Brooks
Keyword(s):  
Body Weight ◽  
Kinase Inhibitors ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Growth Potential ◽  
Cyclin Dependent Kinase ◽  
Body Weight Ratio ◽  
Adaptive Growth ◽  
Adult Rat

We postulated that the cyclin-dependent kinase inhibitors p21 and p27 could regulate the alterations in growth potential of cardiomyocytes during left ventricular hypertrophy (LVH). LVH was induced in adult rat hearts by aortic constriction (AC) and was monitored at days 0, 1, 3, 7, 14, 21, and 42 postoperation. Relative to sham-operated controls (SH), left ventricle (LV) weight-to-body weight ratio in AC increased progressively with time without significant differences in body weight or right ventricle weight-to-body weight ratio. Atrial natriuretic factor mRNA increased significantly in AC to 287% at day 42 compared with SH (P < 0.05), whereas p21 and p27 mRNA expression in AC rats decreased significantly by 58% (P < 0.03) and 40% (P < 0.05) at day 7, respectively. p21 and p27 protein expression decreased significantly from days 3 to 21 in AC versus SH, concomitant with LV adaptive growth. Immunocytochemistry showed p21 and p27 expression in cardiomyocyte nuclei. Thus downregulation of p21 and p27 may modulate the adaptive growth of cardiomyocytes during pressure overload-induced LVH.

Antihypertensive effect of thyroidectomy in SHR: associated changes in heart performance

1986 ◽  
Vol 250 (4) ◽  
pp. H600-H605
Author(s):  
R. L. Rodgers ◽  
J. H. McNeill
Keyword(s):  
Ventricular Hypertrophy ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Body Weight Ratio ◽  
Or Efficiency ◽  
Spontaneously Hypertensive ◽  
Heart Performance ◽  
Rat Hearts ◽  
Wistar Kyoto ◽  
Perfused Hearts

Effects of thyroidectomy (TX; 10 wk) on the performance of perfused hearts from spontaneously hypertensive rats (SHR) were compared with effects on hearts from normotensive Wistar-Kyoto (WKY) controls. TX prevented the development of hypertension in SHR and moderately reduced arterial pressure of WKY, confirming previous observations. TX also reduced heart-to-body-weight ratio (relative left ventricular hypertrophy) but not left-to-right ventricular weight ratio (absolute hypertrophy) of SHR. The performances of euthyroid SHR and WKY hearts were similar to each other. TX reduced maximum left ventricular pulse pressure to the same extent in both strains and had no effect on hydraulic work, O2 consumption, or efficiency of contraction in either strain. However, TX reduced maximum left ventricular +dP/dt of SHR but not of WKY hearts. The results show that hypothyroidism selectively depresses the contractility (LV +dP/dt) of SHR hearts but otherwise has similar effects on the performance of hypertensive and normotensive rat hearts.

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