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Abstract

Dopamine receptor agonists can be useful in the treatment of hypertension or heart failure. Consequently, the present study investigated the hemodynamic profile of the novel dopamine D1/D2 receptor agonist Z1046 in open-chest, pentobarbital-anesthetized swine. Z1046 was administered in a dose of 10 micrograms/kg (n = 9) or 100 micrograms/kg (n = 8), which was injected over 1 minute; hemodynamic responses were studied for 90 minutes after administration. Both doses of Z1046 produced sustained decreases in mean aortic blood pressure (15-20%). The hypotension produced by the lower dose was principally due to a decrease in cardiac output, as the trend toward a lower systemic vascular resistance failed to reach levels of statistical significance. Conversely, the decrease in mean arterial blood pressure produced by the higher dose of Z1046 was mainly due to a decrease in systemic vascular resistance (up to 17%), as the trend toward a decrease in cardiac output at 60 and 90 minutes after administration was not different from the changes in the saline-treated group. Heart rate decreased slightly with both doses of Z1046. Z1046 decreased left ventricular myocardial blood flow (up to 28 +/- 9%, p < 0.05) in parallel with the decrease in myocardial oxygen consumption (up to 24 +/- 7%, p < 0.05), with no change in the transmural distribution of myocardial blood. Z1046 in a dose of 10 micrograms/kg did not produce significant vasodilation of regional vascular beds, but in a dose of 100 micrograms/kg produced vasodilator responses in the small intestine (34 +/- 2% decrease in vascular resistance), spleen (43 +/- 7%), and kidneys (22 +/- 3% all p < 0.05 vs. baseline). In conclusion, Z1046 produced systemic hypotension with negligible reflex activation of sympathetic tone.