Dopamine, dobutamine, and dopexamine. A comparison of renal effects in unanesthetized human volunteers.
BACKGROUND
Recently, dopexamine (DX), which acts via adrenergic beta 2 and dopaminergic DA1 receptors, has been introduced in the treatment of low cardiac output states. However, the renal effects of DX have not been compared to those produced by equipotent inotropic doses of dopamine (DA), which predominantly stimulates DA1 and DA2 receptors, and of dobutamine (DB), which stimulates beta 1 but not DA receptors. The current study tested the null hypothesis that, with equal increases in cardiac output, DX, DA, and DB would have similar effects on renal function.


METHODS
Each drug was given for 2 h on three different occasions to eight normal subjects in doses adjusted to produce a similar 30-35% increase in cardiac output. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were measured as renal clearances of 131I-hippuran and 99mTc-DTPA, respectively. Lithium clearance (CLi) was used as an index of proximal tubular outflow.


RESULTS
Doses of DA, DX, and DB were 2.90 +/- 0.19, 1.00 +/- 0.02, and 4.92 +/- 0.40 microgram.kg-1.min-1, respectively. Dopamine and DX increased ERPF by 23% and 10%, respectively, whereas ERPF remained unchanged during DB. The increase in ERPF was smaller during DX compared with DA. The GFR remained unchanged during DA and DB, but increased during DX (7%). The CLi increased by 35% and 30% during DA and DX, respectively, but was not changed by DB. Calculated absolute proximal reabsorption rate (APR = GFR--CLi) decreased by 13% during DA, but remained unchanged during DB and DX. Dopamine increased sodium clearance (CNa) by 103%, but the changes during DX and DB were not significant. Only DA decreased fractional distal reabsorption (FDRNa = 1--CNa/CLi).


CONCLUSIONS
The findings are consistent with a specific, renal-vasodilating effect of DA and DX. However, in the current doses, this effect of DX was of lesser magnitude compared with that of DA. Only DA significantly increased CNa, and the decreases in APR and FDRNa indicate that an effect on tubular reabsorption rate contributed to the natriuresis.
Olsen
N V
NV
Departments of Anesthesia and Clinical Physiology, Herlev Hospital, Denmark.
Lund
J
J
Jensen
P F
PF
Espersen
K
K
Kanstrup
I L
IL
Plum
I
I
Leyssac
P P
PP
D000328:Adult; D000450:Aldosterone / Q000097:blood; D000758:Anesthesia; D002302:Cardiac Output / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology; D008297:Male; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D013268:Stimulation, Chemical; D014867:Water / Q000378:metabolism
D015259:Dopamine Agents; D014867:Water; C046318:dopexamine; D004280:Dobutamine; D000450:Aldosterone; D012964:Sodium; D012083:Renin; D004298:Dopamine