Diuretic Effects of L-Threo-3, 4-Dihydroxyphenylserine (L-Threo-DOPS) in Anesthetized Rats

[摘要] References(23)Cited-By(1)A synthetic amino acid, L-threo-3, 4-dihydroxyphenylserine (L-threo-DOPS), can be converted to (-)-norepinephrine (NE) by aromatic L-amino acid decarboxy!ase (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-COPS on renal hemodynamics and function in anesthetized rats, and evaluated possible mechanisms of the diuresis. Intravenous infusion of L-threo-DOPS at 120 μg/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 OF during the infusion of L-threo-DOPS. Intrarenal arterial infusion of L-threoDOPS at 20 μg/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 α-adrenoceptor activation.

[学科分类] 药理学