The renal vasodilating effect of dopamine is mediated by calcium flux and prostacyclin release in man.
A low dose of dopamine (DA; 1 microgram/kg.min for 3 h) was infused into 10 normal subjects to determine whether vasodilator prostaglandins might be involved in the vascular action of this vasoactive hormone. Although this DA dose did not alter blood pressure, pulse, or cardiac index, it significantly increased renal blood flow (RBF), as estimated by para-amino-hippurate clearance [1.40 +/- 0.10 (+/- SE) to 1.93 +/- 0.18 L/min.1.73 m2; P less than 0.02]. This increase was due to DA receptor action since it was blocked by metoclopramide, a DA antagonist, and was not altered by prazosin, an alpha-adrenergic antagonist. DA simultaneously increased the urinary excretion rate of 6-keto-PGF1 alpha, a stable metabolite of prostacyclin [PGI2; 79 +/- 16 to 154 +/- 32 ng/g creatinine (2 +/- 0.40 to 3.88 +/- 0.78 pmol/mumol creatinine); P less than 0.02], but there was no change in PGE2 excretion. This dose of DA increased urinary Na+ and K+ excretion and slightly increased creatinine clearance from 0.12 +/- 0.01 to 0.16 +/- 0.02 L/min.1.73 m2 (P less than 0.05). Metoclopramide also blocked the increase in PGI2 excretion, indicating that this increase was due to DA. The relationship between RBF and PGI2 was supported by studies in which either indomethacin or ibuprofen, both cyclooxygenase inhibitors, blocked the increase in both RBF and PGI2 excretion rate. Since some DA actions may be mediated through calcium flux, we also administered nifedipine, a calcium channel-blocking drug, and found that the DA effect on RBF and PGI2 was significantly reduced. These studies suggest that the DA effect on RBF is mediated by calcium flux, which probably activates renal vascular phospholipase, leading to release of arachidonic acid and synthesis of PGI2, a potent vasodilator.
Manoogian
C
C
Department of Medicine, Los Angeles County-University of Southern California School of Medicine 90033.
Nadler
J
J
Ehrlich
L
L
Horton
R
R
D000328:Adult; D002118:Calcium / Q000502:physiology*; D004298:Dopamine / Q000494:pharmacology*; D011464:Epoprostenol / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D014563:Urodynamics / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D011464:Epoprostenol; D002118:Calcium; D004298:Dopamine