Effects of clonidine on central and peripheral nerve tone in primary hypertension

To define the mechanisms whereby clonidine lowers blood pressure, we measured cerebrospinal fluid and plasma levels of norepinephrine, normetanephrine, epinephrine, dopamine, and the dopamine metabolite homovanillic acid in 10 primary hypertensive subjects before and after 3 months of clonidine treatment (mean dose, 0.68 mg/day). Catecholamines were measured by radioenzymatic methods. Cerebrospinal fluid and plasma sampling was performed after subjects had fasted and remained supine overnight, and plasma sampling was repeated 2 hours later, after subjects had ambulated. Supine and upright blood pressure fell, as might be expected. Cerebrospinal fluid levels of norepinephrine and normetanephrine fell significantly, but dopamine and homovanillic acid levels were unchanged. Plasma norepinephrine, normetanephrine, and epinephrine levels decreased 30 to 50%, and supine dopamine levels also fell. The percent fall in supine blood pressure was related to the fall of cerebrospinal fluid and plasma norepinephrine. There were also positive relationships between the decreases of plasma norepinephrine and of normetanephrine and dopamine. The cerebrospinal fluid/plasma norepinephrine ratio was unaffected by clonidine, suggesting that the drug lowered both pools equally. Our findings indicate that clonidine decreases both central and peripheral norepinephrine activity. The dopaminergic activity of cerebrospinal fluid was unaffected by clonidine, and though plasma dopamine levels tended to be lower after treatment, mean plasma prolactin level, an index of dopaminergic activity, was also unchanged. The fall in plasma epinephrine level is probably related to diminished sympathetic adrenomedullary stimulation and is unlikely to contribute to clonidine's antihypertensive action. These results also suggest that measurement of normetanephrine in cerebrospinal fluid and plasma provides a good index of norepinephrine activity.