DNP appears to have a direct action releasing noradrenaline from an extragranular pool in the guinea pig heart, causing a positive inotropic effect.
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Animal data on cardiac effects warrant no clinical extrapolation; leaves open mechanistic roles of amine pools for future translational studies.
Dinitrophenol (DNP) was shown to have cardiac stimulant action on the isolated perfused guinea pig heart. The initial large increase in the force of contraction of the heart was followed by a smaller response which persisted throughout the DNP perfusion. On washout the activity of the heart returned to its previous level. Further DNP perfusion had no effect on the heart even though its amine level was not depleted. However, the positive inotropic effect of DNP reappeared in the heart after perfusion with noradrenaline (NA). Propranolol blocked the cardiac response to DNP. The metabolic uncoupler reduced the NA content in the heart and raised the amine level in the perfusate. The uptake of exogenous NA, and of 14 C‐NA, by the heart was not affected by low and high concentrations of DNP. The results suggest that DNP may have a direct action releasing NA from an extragranular pool.
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Chang et al. (1971) studied this question.
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