8-bromo-cGMP improves the energy charge and redox state of ischaemic rat hearts, likely through enhanced carbohydrate oxidation.
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Hypothesis-generating for cGMP modulation in ischaemic metabolism; leaves open clinical translation.
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.
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K. Laustiola (1985) studied this question.
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