Covariance of plasma free 3-methoxy-4-hydroxyphenethyleneglycol and diastolic blood pressure.

To test the acute effects of clonidine on plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG), the major metabolite of brain norepinephrine (NE), and to examine the relationship between plasma MHPG and concurrently measured blood pressure variables, we performed a series of 31 double blind, placebo controlled, test days in which clonidine (1 and 5 micrograms/kg) or placebo was administered (p.o. at 9:00 a.m.) to six fasting normotensive male subjects. Three h following the 5 micrograms/kg clonidine dose, plasma MHPG reached a nadir significantly below both baseline and placebo levels (P less than 0.05). Mean MHPG concentrations were significantly correlated with diastolic blood pressure (sitting: r = 0.46, df = 88, P less than 0.00001; standing r = 0.49, df = 73, P less than 0.00001). Unexpectedly, this relationship was independent of clonidine dose and sampling time. Under drug-free conditions, the correlation between plasma free MHPG and diastolic blood pressure remained significant (sitting: r = 0.43, df = 40, P = 0.003; standing: r = 0.46, df = 33, P = 0.006). The findings are considered in light of evidence implicating brain NE systems in the regulation of blood pressure.