Cerebrospinal fluid norepinephrine levels in essential hypertension: effects of drug treatment and withdrawal.
Measurements of cerebrospinal fluid (CSF) catecholamines (CA) were made in an attempt to estimate the activity of central CA neurons in essential hypertension (EHT). CSF norepinephrine (NE), epinephrine (EPI), and dopamine (DA) levels were measured in 12 normotensive (age 36 +/- 3 years; SBP = 116 +/- 4 and DBP = 79 +/- 4 mm Hg) and in 12 EHT (age 41 +/- 2 years; CSF NE levels were twofold higher in EHT (240 +/- 23 pg/ml) than in normotensive subjects (127 +/- 28 pg/ml). Very low EPI and DA levels were observed in both groups of patients. The results suggest that central (spinal?) noradrenergic activity is increased in patients with EHT. In a second study we evaluated the effects of clonidine treatment for 2 weeks (150 micrograms t.i.d.) on CSF NE in EHT. Clonidine reduced pretreatment BP and CSF NE levels by 27% (p less than 0.05) and 39% (p less than 0.01), respectively. The results of the study indicate that central noradrenergic activity is reduced during clonidine treatment. A third group of experiments was designed to compare the effects of clonidine with those of propranolol treatment in patients with EHT. CSF NE measurements were made after 1 month of treatment with 0.36 +/- 0.07 mg of clonidine daily or 160 mg of propranolol daily. CSF NE levels were significantly lower in the clonidine group (p less than 0.01). Seventy-two hours after abrupt discontinuation of clonidine or propranolol treatment, BP returned to pretreatment levels. However, CSF NE showed a threefold increase after clonidine withdrawal, and no change after propranolol withdrawal. CSF EPI was not affected by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Cubeddu
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Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27514.
Hoffman
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D000328:Adult; D003000:Clonidine / Q000627:therapeutic use; D004298:Dopamine / Q000097:blood; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D008750:Methyldopa / Q000627:therapeutic use; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood / Q000134:cerebrospinal fluid*; D011433:Propranolol / Q000627:therapeutic use; D011897:Random Allocation
D008750:Methyldopa; D011433:Propranolol; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine