Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension

Abstract

We infused tracer-labeled l-[3H]-norepinephrine, d-[14C]norepinephrine, and d,l-[3H]-isoproterenol simultaneously into patients with essential hypertension and into normotensive control subjects, in order to determine whether abnormalities in the disappearance kinetics of these substances characterized the hypertensive patients. The mean preinfusion venous plasma norepinephrine concentration was somewhat higher in the hypertensive group (260 vs. 194 pg/ml, P = 0.06), but the groups did not differ in the disappearance kinetics of l- or d-norepinephrine or of isoproterenol. Preinfusion plasma norepinephrine was significantly positively correlated with calculated spillover rates in both the hypertensive and normotensive groups, but not with norepinephrine clearances. The d/l ratio in plasma norepinephrine was the same as in the infusate during and after the infusion, even after pretreatment with the neuronal norepinephrine uptake blocker, desipramine. Because isoproterenol is not taken up by nerve endings, the ratio of [3H]isoproterenol to l-[3H]norepinephrine increased after the infusion ended. This increase was almost completely abolished by pretreatment with desipramine. These results indicate that (a) increased plasma norepinephrine levels seen in some patients with essential hypertension result from increased sympathetic neural activity and not from decreased clearance of norepinephrine, (b) changes in the isoproterenol/norepinephrine ratio after simultaneous infusion of both provide an index of neuronal norepinephrine uptake in man, and (c) neuronal norepinephrine uptake is not stereospecific.