The Relationships of Free to Conjugated Normetanephrine in Plasma and Spinal Fluid of Hypertensive Patients*

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Abstract
The concentrations of free and total normetanephrine (NMN) were determined in the plasma of normotensives and patients with primary hypertension and pheochromocytoma. NMN values were measured in the cerebrospinal fluid (CSF) of patients. Free and conjugated NMN, the latter after acid hydrolysis, were assayed using S-adenosylmethionine in the presence of phenylethanolamine-iV-methyltransferase to form labeled metanephrine. The conjugates of NMN were present in plasma as sulfates principally, as they were also liberated with arylsulfatase. Free and conjugated NMN levels were 117 ± 10 and 1417 ± 109 ng/liter, respectively in plasma of normotensives. The mean ratio of the content of conjugated to free NMN was 14.9 ± 1.8 (mean ± SEM). The contents of free and conjugated NMN were 155 ± 33 and 1670 ± 320 ng/liter in primary hypertensives, respectively, and the ratio of conjugated to free NMN was 18.5 ± 3.3. These values did not differ significantly from those in normotensives. The contents of free and total NMN in the plasma of patients with pheochromocytoma were 50- to 60- fold greater than values in normotensives and primary hypertensives. The mean ratio of conjugated to free NMN in the plasma of patients with pheochromocytoma was similar to those in normotensives and primary hypertensives. The contents of free and conjugated NMN in the CSF of patients with pheochromocytoma exceeded those in primary hypertensives (P<0.01 and P<0.001). Further, the ratio of conjugated to free NMN in CSF was increased in patients with pheochromocytoma (33.9 ± 8.1) compared to that primary hypertensives (8.3 ± 2.3; P<0.001). The measurement of NMN in plasma and CSF may help characterize sympathetic nerve tone in patients with primary hypertension to elucidate the pathophysiology of the elevated blood pressure.