Long-term effects of diadenosine polyphosphates on blood pressure, heart rate, glucose and insulin levels of rats
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Using an infusion (0.29 μl per hour of a solution of diadenosine polyphosphates (ApnAs) and ATP (80 mg/kg b.w.) drug per 100 μl over two weeks) by implantation of Alzet® pumps, the long-term physiological role of ApnAs including adaptation was investigated. Ap4A increased blood glucose, decreased plasma insulin, decreased blood pressure (systolic and mean) and increased heart rate. These effects were not identical to those of ATP (decrease of blood glucose, increase in plasma insulin, decrease in blood pressure and increase in heart rate); thus the Ap4A effect is not mediated by this degradation product. Both ApsA and ApeA had the same effect as Ap4A with respect to blood glucose and plasma insulin, albeit behaving differently from Ap4A in that they increased blood pressure and decreased heart rate. All observed and above mentioned results when expressed as AUC (area under the curve over 14 days) were significantly different from control (saline infused by an Alzet® pump). The effects leveled off when the reservoir of the pump was empty after 14 days. In conclusion: 1) either diadenosine polyphosphate induces a diabetic situation after at least two days (first time point of measurement after surgery); however, while Ap4A decreases blood pressure and increases heart rate, ApsA and ApeA have opposite effects in this respect. 2) The effects observed are not mediated by the degradation product ATP. 3) No adaptation was observed. 4) Diadenosine polyphosphates may be considered to be pathophysiological factors with respect to diabetes and blood pressure control. Antagonists should be a valuable tool for further research.