8-bromocyclic-gmp and Coronary-Disease

The effects of 8-bromo cyclic GMP (1 X 10(-5)M) on the levels of lactate, NAD+, NADH, AMP, ADP, ATP, creatine phosphate (CrP) and creatine were studied in the ischaemic Langendorff-perfused rat heart. The NAD+/NADH ratio and the energy charge were also calculated. The dependence of the effect of 8-bromo-cGMP on substrate availability was also studied by adding pyruvate (5 mM and 10 mM) to the perfusate, and by comparing the changes to those during perfusion with glucose alone. When glucose (11 mM) was used as the only substrate, 8-bromo-cGMP administration resulted during ischaemia, in a decrease of the NADH level, and in an increase of the energy charge. When pyruvate (5 mM) was added to the perfusate, 8-bromo-cGMP administration resulted in an increase in the NAD+/NADH ratio and in an increase of the energy charge. When the pyruvate concentration was further increased (10 mM), no changes were seen in the beforementioned variables after 8-bromo-cGMP administration. It is concluded that the effects of 8-bromo-cGMP may be exerted by an enhancement of carbohydrate oxidation.

Topics: Animals; Coronary Disease; Cyclic GMP; Energy Metabolism; Glucose; In Vitro Techniques; Lactates; Lactic Acid; Male; Myocardium; NAD; Oxidation-Reduction; Perfusion; Pyruvate Dehydrogenase Complex; Pyruvates; Pyruvic Acid; Rats; Rats, Inbred Strains

The effects of 8-bromo-cGMP on tissue lactate and NADH levels were studied under conditions of high oxygen saturation (95-100%) and hypoxia (50%) in spontaneously beating rat atria. The induction of hypoxia caused a rapid decline in contractility with a simultaneous increase in tissue lactate and NADH. 8-bromo-cGMP (10(-4) mol/l) prevented the accumulation of lactate occurring during hypoxia. It also lowered the level of lactate during high oxygen saturation. Furthermore, 8-bromo-cGMP inhibited the hypoxia-induced increase in NADH and lowered the level of NADH in high oxygen saturation. 8-bromo-cGMP did not affect contractility or heart rate during hypoxia. It is concluded that cGMP may influence the redox-state and metabolism in a direction which is beneficial for the hypoxic myocyte. It is also suggested that antianginal nitro compounds which enhance the level of cGMP might exert an effect similar to that of 8-bromo-cGMP.

Topics: Animals; Coronary Disease; Cyclic GMP; In Vitro Techniques; Lactates; Lactic Acid; Male; Myocardium; NAD; Oxygen Consumption; Rats; Rats, Inbred Strains