Reduction in human urinary MHPG excretion by guanethidine: Urinary MHPG as index of sympathetic nervous activity

The norepinephrine metabolites methoxyhydroxyphenyl glycol (MHPG) and vanillylmandelic acid (VMA) were measured in the urine of hypertensive subjects before and during adminstration of guanethidine, a peripheral sympatholytic agent which does not cross the blood-brain barrier or deplete adrenal catecholamines. Dosages of guanethidine (1.2 mg/kg/day) sufficient to cause at least a 20 torr reduction in standing systolic blood pressure caused a mean 63% (maximum of 68%) reduction in urinary MHPG excretion (p=0.01) while only causing a mean 37% (maximum of 44%) reduction (p<0.005) in excretion of VMA. These results indicate that MHPG in human urine, as in lower animals, is predominantly the product of peripheral sympathetic nervous system, rather than central nervous system nonrepinephrine metabolism. Urinary MHPG is more sensitive to specific sympatholytic therapy than is urinary VMA, and may be a useful index of sympathetic nervous activity.