title: Cardiovascular actions of the dopamine receptor agonist Z1046 in swine.
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.
authors.affiliation: Laboratory for Experimental Cardiology, Erasmus University Rotterdam, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Duncker
authors.forename: J R
authors.initials: JR
authors.lastname: van Meegen
authors.forename: P D
authors.initials: PD
authors.lastname: Verdouw
mesh_terms: D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009284:Naphthols / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D018491:Dopamine Agonists; D009284:Naphthols; C105333:Z1046