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

F. Tomita, A. L. Bassett, Robert J Myerburg, S. Kimura

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Sarcoplasmic reticulum (SR) Ca2+ uptake is reduced in the hypertrophied ventricle. To determine whether events initiated by β-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 MCa2+ 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 Ca2+- 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. We conclude that there is a reduced SR responsiveness to cAMP in hypertrophy and that this reduction in Ca2+ accumulation contributes to diminished β-adrenergic responsiveness in hypertrophy.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume266
Issue number2 35-2
StatePublished - Jan 1 1994

Fingerprint

Sarcoplasmic Reticulum
Caffeine
Muscles
Adrenergic Agents
Hypertrophy
Pressure
Abdominal Aorta
Saponins
Ventricular Pressure
Cyclic AMP
Ligation
Body Weight
Weights and Measures

Keywords

  • calcium sensitivity
  • calcium uptake
  • chronic pressure overload
  • sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology

Cite this

Diminished effect of cAMP on Ca2+ accumulation in skinned fibers of hypertrophied rat heart. / Tomita, F.; Bassett, A. L.; Myerburg, Robert J; Kimura, S.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 266, No. 2 35-2, 01.01.1994.

Research output: Contribution to journalArticle

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abstract = "Sarcoplasmic reticulum (SR) Ca2+ uptake is reduced in the hypertrophied ventricle. To determine whether events initiated by β-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 MCa2+ 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 Ca2+- 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. We conclude that there is a reduced SR responsiveness to cAMP in hypertrophy and that this reduction in Ca2+ accumulation contributes to diminished β-adrenergic responsiveness in hypertrophy.",
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