cGMP prevents delayed relaxation at reoxygenation after brief hypoxia in isolated cardiac myocytes

A. M. Shah, H. S. Silverman, E. J. Griffiths, H. A. Spurgeon, E. G. Lakatta

Research output: Contribution to journalArticle

Abstract

Previous studies in isolated cardiac myocytes suggest that impaired relaxation during reoxygenation after brief hypoxia results from abnormal Ca2+-myofilament interaction. Recent studies indicate that guanosine 3',5'- cyclic monophosphate (cGMP)elevating interventions selectively enhance myocardial relaxation. We investigated the effect of 8-bromoguanosine 3',5'- cyclic monophosphate (8-BrcGMP) on posthypoxic relaxation in single rat myocytes, with simultaneous measurement of contraction and intracellular Ca2+ (indo 1 fluorescence). In control myocytes (n = 11), reoxygenation after 10 min of hypoxia markedly prolonged time to peak shortening (+36.5 ± 4.2%) and half-relaxation time (+75.7 ± 11.3% cf. normoxic values; both P < 0.001) and reduced diastolic length but did not change cytosolic Ca2+. Under normoxic conditions, 50 μM 8-BrcGMP slightly reduced time to peak shortening and half-relaxation time and increased diastolic length but did not alter cytosolic Ca2+. In the presence of 8-BrcGMP, there was no posthypoxic delay in twitch relaxation nor was there a decrease in diastolic length (half-relaxation time -5.8 ± 3.3% cf. normoxic values; P < 0.05 cf. control group; n = 11). Cytosolic Ca2+ remained unaltered. Thus, 8-BrcGMP fully prevents impaired posthypoxic relaxation in isolated cardiac myocytes, probably by altering Ca2+-myofilament interaction.

Original languageEnglish (US)
Pages (from-to)H2396-H2404
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume268
Issue number6 37-6
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • cardiac contraction
  • diastole
  • myofilament
  • reperfusion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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