THE MECHANISMS UNDERLYING HEART STIMULATION BY DOPAMINE, WITH SPECIALREFERENCE TO DIRECT AND INDIRECT BETA-ADRENOCEPTOR STIMULATION

1. The positive chronotropic and norepinephrine-releasing effects of d opamine were examined in the isolated guinea pig heart, using the Lang endorff model. 2. The released norepinephrine was estimated from the n orepinephrine concentration measured in the post-perfusion solution us ing HPLC. 3. The dose-response curve for dopamine to stimulate the hea rt rate (HR) closely resembled that for the norepinephrine release. A selective beta(1) antagonist bisoprolol completely abolished the posit ive chronotropic effect, but did not affect ?he norepinephrine release . 4. The HR increase in response to 3 mu mol/L dopamine was 54 +/- 15 % (n=14) of the control in normal hearts. The response was decreased t o 15 +/- 7 % (n=6) by pretreatment with reserpine. 5. A D-1 antagonist , SKF83742, (3 mu mol/L) shifted the dose-response curve for the dopam ine-induced norepinephrine release toward the right, indicating the in volvement of D-1-like dopamine receptors. 6. Voltage clamp experiments using single cells isolated from the right atrium revealed that dopam ine is a weak partial agonist for beta adrenoceptors. Dopamine stimula ted the L-type Ca2+ current with a threshold concentration of 3 mu mol /L. 7. These findings indicate the important role of the norepinephrin e release in the stimulation of beta adrenoceptors by dopamine at clin ically relevant concentrations.