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

Abstract

A B S T R A C T We infused tracer-labeled 1-[3H]-norepinephrine, d-['4C]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 1-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 dli 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.

Obesity Paradox in Hypertension

“…A fault in this process would be expected to augment the sympathetic neural signal. Earlier reports from 3 laboratories [33][34][35] suggested that impairment of norepinephrine reuptake was present in essential hypertension, although the evidence was not totally conclusive. More definitive evidence of impaired neuronal reuptake of norepinephrine emerged with the application of norepinephrine tracer kinetics across the heart in hypertensive patients.…”

Measurement of regional neuronal removal of norepinephrine in man.

“…After stopping a simultaneous infusion of tracerlabeled NE and ISO, the ratio of radioactivity in ISO to that in NE increases rapidly, and the increase in this ratio is abolished by desipramine (8). The rate of increase in the ISO: NE ratio is independent of dilution and therefore has been suggested as a measure of Uptake, (8).…”

“…With the subject supine, a plastic catheter was inserted percutaneously into the brachial artery after local infiltration of the overlying skin using 1% lidocaine. A (9) and was modified for the purposes of the experimental design used in this study (8). The procedure allowed complete separation of the radioactivity in the chromatographic peak for NE from the radioactivity in the chromatographic peak for ISO.…”

“…3 h before this second infusion, the subjects took 125 mg desipramine by mouth. This was a dose that we previously found to abolish completely the increase in the ISO:NE ratio after stopping the infusion (8). Two other subjects were pretreated with desipramine before their only infusion.…”

Plasma norepinephrine and dihydroxyphenylglycol in essential hypertension.

“…A reduced plasma DOPEG clearance in essential hypertension would lead to an increase in the desipramine-sensitive as well as desipramineresistant component of plasma DOPEG and, thus, could help to explain our results. However, although nothing is known about the plasma clearance of DOPEG in humans, several authors have demonstrated not only the plasma clearance of norepinephrine to be similar in hypertensive and normal subjects, 22 -32 -34 but also those of epinephrine 35 and isoprenaline. 34 That is why we consider it rather unlikely that hypertensive and normotensive subjects differ substantially with respect to the plasma clearance of DOPEG.…”