Comparative hemodynamic effects of hypotension induced by diadenosine tetraphosphate (AP₄A) and ATP in dogs

ATP and diadenosine tetraphosphate (AP₄A) have been shown to produce vasodilation mediated by P₁- and P₂-purinoceptor, respectively. The differing mechanisms involved in this vasodilating activity may induce different systemic hemodynamic changes. We compared the hemodynamic effects of AP₄A-induced hypotension with those induced by ATP. Fourteen mongrel dogs were anesthetized with 0.87% halothane in oxygen (1 MAC). After the baseline period, mean arterial pressure was reduced to 60 mmHg for 60 min by the infusion of AP₄A or ATP. The ATP- and AP₄A-induced hypotension resulted in a maximum reduction in systemic vascular resistance of 43% and 46%, respectively (P<0.01), associated with a significant increase in stroke volume index. With ATP, a 20% of maximum increase (P<0.05) in cardiac index (CI) was observed during the induced hypotension. In contrast, AP₄A-induced hypotension did not result in any changes in CI throughout the observation period. The varying results concerning CI during the ATP- and AP₄A-induced hypotension were probably due to differences in ventricular filling pressure, since AP₄A-induced hypotension was associated with decreases (P<0.01) in both right atrial and pulmonary capillary wedge pressures, whereas neither of these variables significantly changed with ATP. The hypotension induced by either ATP or AP₄A was associated with a significant decrease in heart rate (HR). However, both the magnitude and duration of decreases in HR due to ATP-induced hypotension were more pronounced than those seen with AP₄A. In conclusion, while both drugs were equally capable of inducing hypotension, our results suggest that AP₄A was more suitable for induced hypotension because of its potent vasodilatory action with venodilation and less negative chronotropic action.