Norepinephrine precursor therapy in neurogenic orthostatic hypotension
Norepinephrine precursor therapy in neurogenic orthostatic hypotension
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DOI：
10.1161/01.cir.0000083721.49847.d7
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发表时间：
2003-08-12
期刊：
影响因子：
37.8
通讯作者：
Freeman, R
中科院分区：
文献类型：
--
作者：
Kaufmann, H;Saadia, D;Freeman, R
Background-In patients with neurogenic orthostatic hypotension (NOH), the availability of the sympathetic neurotransmitter norepinephrine ( NE) in the synaptic cleft is insufficient to maintain blood pressure while in the standing posture.Methods and Results-We determined the effect of oral administration of the synthetic amino acid L-threo-3,4-dihydroxyphenylserine (L-DOPS), which is decarboxylated to NE by the enzyme L-aromatic amino acid decarboxylase (L-AADC) in neural and nonneural tissue, on blood pressure and orthostatic tolerance in 19 patients with severe NOH ( 8 with pure autonomic failure and 11 with multiple-system atrophy). A single-blind dose-titration study determined the most appropriate dose for each patient. Patients were then enrolled in a double-blind, placebo-controlled, crossover trial. L-DOPS significantly raised mean blood pressure both supine ( from 101 +/- 4 to 141 +/- 5 mm Hg) and standing ( from 60 +/- 4 to 100 +/- 6 mm Hg) for several hours and improved orthostatic tolerance in all patients. After L-DOPS, blood pressure increases were closely associated with increases in plasma NE levels. Oral administration of carbidopa, which inhibits L-AADC outside the blood-brain barrier, blunted both the increase in plasma NE and the pressor response to L-DOPS in all patientsConclusions-Acute administration of L-DOPS increases blood pressure and improves orthostatic tolerance in patients with NOH. The pressor effect results from conversion of L-DOPS to NE outside the central nervous system.
