Diuretic effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) in anesthetized rats.
A synthetic amino acid, L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), can be converted to (-)-norepinephrine (NE) by aromatic L-amino acid decarboxylase (AADC) in various mammalian tissues. Recent studies have indicated the pressor and diuretic effects of L-threo-DOPS. In this study, we examined the effects of L-threo-DOPS on renal hemodynamics and function in anesthetized rats, and evaluated possible mechanisms of the diuresis. Intravenous infusion of L-threo-DOPS at 120 micrograms/kg/min exerted a significant increase in mean arterial pressure (MAP). There was a slight but nonsignificant decrease in renal blood flow (RBF). Although the glomerular filtration rate (GFR) remained at a constant level, urine flow (UF) and urinary sodium excretion (UNaV) increased significantly during the drug infusion. Pretreatment with AADC inhibitor, benserazide, completely blocked both the pressor and diuretic effects of L-threo-DOPS. When the renal perfusion pressure was protected from the pressor effect of the drug by using a Blalock clamp, the drug-induced diuresis was abolished. The diuretic effect of L-threo-DOPS was markedly attenuated by the administration of phentolamine. There was a positive correlation between plasma NE concentration and UF during the infusion of L-threo-DOPS. Intrarenal arterial infusion of L-threo-DOPS at 20 micrograms/kg/min was without effect on renal function. These results indicate that diuresis and natriuresis induced by L-threo-DOPS are dependent on the pressor effect of NE via peripheral alpha-adrenoceptor activation.
Morimoto
S
S
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Ohyama
T
T
Shinyama
H
H
Ichihara
T
T
Takahashi
Y
Y
Hisaki
K
K
D000758:Anesthesia; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001545:Benserazide / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D015103:Droxidopa / Q000008:administration & dosage / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012694:Serine / Q000031:analogs & derivatives*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004232:Diuretics; D012694:Serine; D001545:Benserazide; D015103:Droxidopa; D009638:Norepinephrine; D010646:Phentolamine