Cyclic gmp prevents delayed relaxation at reoxygenation following brief
hypoxia in isolated cardiac myocytes.
Shah, Ajay M., Md, Mrcp, Howard S. Silverman, Md, Elinor J. Griffiths, Phd,
Harold A. Spurgeon, Phd, and Edward G. Lakatta, Md.
Laboratory of Cardiovascular Science (AMS, HSS, HAS, EGL), Gerontology
Research Center, NIA, National Institutes of Health, & the Department of
Medicine (HSS, EG), Division of Cardiology, Johns Hopkins Medical
Institutions, Baltimore, Md; & the Department of Cardiology (AMS), University
of Wales College of Medicine, Cardiff, UK.
APStracts 2:0012H, 1995.
Previous studies in isolated cardiac myocytes suggest that impaired relaxation
during reoxygenation following brief hypoxia results from abnormal Ca2+
-myofilament interaction. Recent studies indicate that cyclic GMP-elevating
interventions selectively enhance myocardial relaxation. We investigated the
effect of 8-bromo cyclic GMP (8bcGMP) on post-hypoxic 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 hypoxia markedly prolonged time to peak shortening (+36.5+/-4.2%) and
relaxation half-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, 8bcGMP (50 [mu]M) slightly reduced time to peak shortening and
relaxation half-time, and increased diastolic length, but did not alter
cytosolic Ca2+. In the presence of 8bcGMP, there was no post-hypoxic delay in
twitch relaxation nor decrease in diastolic length (relaxation half-time
-5.8+/-3.3% cf. normoxic values; p<0.05 cf. control group; n=11). Cytosolic
Ca2+ remained unaltered. Thus, 8bcGMP fully prevents impaired post-hypoxic
relaxation in isolated cardiac myocytes, probably by altering Ca2+
-myofilament interaction.
Received 11 January 1994; accepted in final form 11 January 1995.
APS Manuscript Number H30-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 February 1995.