CGMP PREVENTS DELAYED RELAXATION AT REOXYGENATION AFTER BRIEF HYPOXIAIN ISOLATED CARDIAC MYOCYTES

Previous studies in isolated cardiac myocytes suggest that impaired re laxation during reoxygenation after brief hypoxia results from abnorma l 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-bromog uanosine 3',5'-cyclic monophosphate (8-BrcGMP) on posthypoxic relaxati on in single rat myocytes, with simultaneous measurement of contractio n 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 len gth but did not change cytosolic Ca2+. Under normoxic conditions, 50 m u M 8-BrcGMP slightly reduced time to peak shortening and half-relaxat ion time and increased diastolic length but did not alter cytosolic Ca 2+. In the presence of 8-BrcGMP, there was no posthypoxic delay in twi tch relaxation nor was there a decrease in diastolic length (half-rela xation time -5.8 +/- 3.3% cf. normoxic values; P < 0.05 cf. control gr oup; n = 11). Cytosolic Ca2+ remained unaltered. Thus, 8-BrcGMP fully prevents impaired posthypoxic relaxation in isolated cardiac myocytes, probably by altering Ca2+-myofilament interaction.