Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension.
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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.
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The neurochemical indices used in this study were previously shown to be sensitive markers of reduced neuronal NE reuptake after pharmacological uptake blockade with desipramine and in patients with transporter absence accompanying pure autonomic failure.
“The indices chosen for investigation were those previously shown to be sensitive markers of reduced neuronal NE reuptake in situations of reuptake impairment, specifically after pharmacological uptake blockade with the tricyclic antidepressant desipramine, 5,7,8 and in patients with transporter absence accompanying sympathetic nerve degeneration (pure autonomic failure).11”
From Phenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension (2000) · cites this paper as [7]
In earlier studies, the half-time of the rapid disappearance phase of tritiated NE removal from plasma after infusion was prolonged in some patients with essential hypertension.
“In these earlier studies, the half-time of the rapid disappearance phase of tritiated NE removal from plasma on termination of an intravenous infusion of the tracer, which is primarily, but not exclusively, dependent on neuronal NE uptake was found to be prolonged in some patients with essential hypertension.[5][6][7]”
From Phenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension (2000) · cites this paper as [7]
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References 30 · Cited by 71
- Authors
- Goldstein, D. S., Horwitz, D., Keiser, H. R., Polinsky, R. J., & Kopin, I. J.
- Affiliations
- National Institutes of Health (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1983-11-01
- Volume
- 72
- Issue
- 5
- Pages
- 1748-1758
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC370463
- OpenAlex
- W2161530273
- Cited by
- 71
- References
- 30
- Citations by year
- 2026: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2014: 1 · 2013: 1
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- essential hypertension, norepinephrine, isoproterenol, desipramine, sympathetic activity, norepinephrine clearance, plasma norepinephrine, stereoisomer ratio
- MeSH terms
- Adult, Carbon Radioisotopes, Desipramine, Humans, Hypertension, Isoproterenol, Metabolic Clearance Rate, Middle Aged, Norepinephrine, Stereoisomerism, Tritium
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