The effects of different doses of dopamine and domperidone on increases of plasma norepinephrine induced by cold pressor test in normal man.
The effect of dopamine 1 and 3 micrograms/kg/min i.v., of dopamine 1 and 3 micrograms/kg/min i.v. combined with domperidone 30 mg per os and of placebo infusion on plasma norepinephrine concentration before and during sympathetic stimulation by a cold pressor test was investigated in 10 healthy volunteers (1 female, 9 males, mean age 28, range 19-41). Dopamine 1 microgram/kg/min resulted in a blunting of the rise in plasma norepinephrine concentration during the cold pressor test, compared with placebo infusion. The addition of domperidone to dopamine 1 microgram/kg/min abolished this effect. Plasma norepinephrine levels during dopamine 3 micrograms/kg/min infusion, both with and without domperidone, were not different from placebo, but significantly higher compared to dopamine 1 microgram/kg/min infusion. Dopamine 1 and 3 micrograms/kg/min infusion, both with and without domperidone resulted in a blunted increase in blood pressure compared to placebo infusion. Dopamine 1 microgram/kg/min infusion resulted in a lower systolic blood pressure during the cold pressor test compared to dopamine 3 micrograms/kg/min infusion. No significant changes in heart rate occurred during the cold pressor test comparing the different circumstances. We conclude that in healthy volunteers only dopamine 1 microgram/kg/min, but not dopamine 3 micrograms/kg/min, blunts the increase in plasma norepinephrine concentration during a cold pressor test; this effect is abolished by pretreatment with domperidone. We presume that for dopamine 1 microgram/kg/min the inhibitory effects of presynaptic DA-2 receptor or alpha-2 adrenoceptor stimulation on plasma norepinephrine concentration predominate. When dopamine 3 micrograms/kg/min is infused, the inhibitory effects might be counteracted by uptake-1 inhibition or enhanced synthesis and release of norepinephrine, either directly or indirectly.
Department of Internal Medicine, University Hospital Groningen, The Netherlands.
A G
AG
Lieverse
J D
JD
Lefrandt
A R
AR
Girbes
A J
AJ
Smit
W D
WD
Reitsma
D000328:Adult; D003080:Cold Temperature; D018592:Cross-Over Studies; D004294:Domperidone / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D011312:Pressure; D016037:Single-Blind Method; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D018492:Dopamine Antagonists; D004294:Domperidone; D004298:Dopamine; D009638:Norepinephrine