Cerebrospinal Fluid Norepinephrine Levels in Essential Hypertension: Effects of Drug Treatment and Withdrawal

Abstract

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; SBP = 163 ± 5 and DBP = 107 ± 3 mm Hg) subjects. 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 μg t.i.d.) on CSF NE in EHT. Clonidine reduced pretreatment BP and CSF NE levels by 27% (p < 0.05) and 39% (p < 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 < 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. These results suggest that neither the reduction in BP produced by propranolol nor the BP raise after propranolol discontinuation is mediated by changes in the central (spinal?) noradrenergic activity. For clonidine, on the other hand, treatment and withdrawal lead to marked changes in CSF NE levels.