Analysis of the effects of dopamine-1 and dopamine-2 receptor agonists on coronary flow

The coronary flow (CF) at constant perfusion pressure and other hemodynamic variables were measured in anesthetized open-chest dogs. At the same doses of 20, 100, 500 and 2000 nM, the dopamine-1 receptor agonist, fenoldopam, was much more potent than dopamine-2 receptor agonist, N-n-propyl-N-n-butyl dopamine (PBDA), in increasing CF. Under conditions of constant systemic arterial pressure, fenoldopam produced a dose-related increase in maximal +dp/dt (dp/dt) and CF. After adrenergic blockade (combined alpha- and beta-adrenoceptor blockade), however, both cardiac and coronary effects of fenoldopam were greatly attenuated. The coronary effects of both dopamine agonists under uncontrolled arterial pressure were apparently greater than those under constant arterial pressure. Under conditions of uncontrolled arterial pressure and after adrenergic blockade, fenoldopam induced a dose-related decrease in mean arterial pressure (MAP) and corresponding increase in CF. SCH23390 and domperidone markedly inhibited the coronary effects of fenoldopam and PBDA, respectively. Our data suggest that the coronary effects of fenoldopam are predominantly secondary to the fenoldopam-induced decrease in total peripheral resistance (TPR) at small doses and to its positive inotropic action at large doses, while the primary dopaminergic coronary vasodilation plays only a minor role and therefore cannot be of physiological importance in regulating CF.