Role of adrenoceptors and dopamine receptors in modulating left ventricular diastolic function.
Although both dopamine and dobutamine are potent positive inotropic agents, multiple studies indicate that dopamine may produce a rise in left ventricular (LV) filling pressure, while dobutamine often has the opposite effect. To ascertain the pharmacological and hemodynamic mechanisms responsible for the elevation in LV filling pressure observed with dopamine, we administered incremental infusions (2, 4, and 6 micrograms/kg/min) of dopamine to 18 open-chest, anesthetized dogs in the presence and absence of rauwolscine (selective alpha 2-adrenoceptor antagonist) (n = 7), terazosin (selective alpha 1-antagonist) (n = 6), and domperidone (selective dopamine2 antagonist) (n = 5), while measuring pressures in the LV and left atrium and changes in dimension in the LV short-axis (with ultrasonic piezo crystals). Dobutamine (2, 4, and 6 micrograms/kg/min) was infused in five additional dogs before and after administration of rauwolscine. The time constant of isovolumic pressure decay, peak lengthening rate (mm/sec), LV end-diastolic pressure, and diastolic pressure-dimension relation were computed. A significant elevation in LV end-diastolic pressure and a parallel increase in LV end-diastolic chamber size was observed with dopamine, while a decline in LV end-diastolic pressure occurred with dobutamine. Yet both dopamine and dobutamine caused a dose-related acceleration of pressure decay and augmentation of peak lengthening rate. Furthermore, heart rate declined during the administration of dopamine but rose with dobutamine. In the presence of either rauwolscine or terazosin, dopamine infusion resulted in a positive chronotropic effect and dose-dependent reductions in LV end-diastolic pressure and end-diastolic chamber dimension; arterial pressure fell only after terazosin administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Lang
R M
RM
Section of Cardiology, University of Chicago, IL 60637.
Carroll
J D
JD
Nakamura
S
S
Itoh
H
H
Rajfer
S I
SI
D000818:Animals; D003971:Diastole / Q000187:drug effects*; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011954:Receptors, Dopamine / Q000502:physiology*; D013599:Systole / Q000187:drug effects; D016276:Ventricular Function; D015016:Yohimbine / Q000494:pharmacology
D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D015016:Yohimbine; D004280:Dobutamine; D004294:Domperidone; C041226:Terazosin; D004298:Dopamine; D011224:Prazosin