Evidence for functional α2-adrenoceptors on vascular sympathetic nerve endings in the human forearm

E. Grossman, P. C. Chang, A. Hoffman, M. Tamrat, D. S. Goldstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The role of α2-adrenoceptors on vascular sympathetic nerve endings in modulating release of the sympathetic neurotransmitter norepinephrine (NE) in humans was examined by measuring the regional rate of appearance of NE in forearm venous plasma (forearm NE spillover [FSO]) in 32 healthy volunteers during intra-arterial infusion of drugs acting at adrenoceptors or directly on vascular smooth muscle. Simultaneous intra-arterial infusions of tracer amounts of [3H]NE were used to calculate the extraction rate of NE in the forearm. Methoxamine or propranolol with epinephrine (PRO+EPI) was used to stimulate α-adrenoceptors, yohimbine was used to inhibit α-adrenoceptors, and sodium nitroprusside (NIP) was used to produce increases in forearm blood flow directly. Sympathetic efferent activity was manipulated by systemic intravenous infusions of NIP or trimethaphan. Yohimbine and NIP increased and PRO+EPI and methoxamine decreased NE FSO, without effects on systemic blood pressure, heart rate, or arterial levels of catechols. Changes in FSO were flow dependent; therefore, the slope of the relation between the changes in FSO and forearm blood flow was used to evaluate the effects of each drug on regional sympathoneural activity. During administration of yohimbine, the mean slope of the relation between the change in estimated FSO and the change in forearm blood flow was about four times that of the mean slope during administration of NIP (F = 6.35, p < 0.05). The slopes of the relations between changes in FSO and forearm blood flow were unaffected by systemic trimethaphan or NIP infusion, indicating that the activity of α2-adrenoceptors was not altered during inhibition or reflexive stimulation of sympathetic outflow. The results suggest that α2-adrenoceptors modulate release of NE from vascular sympathetic nerve endings in humans and that the function of these receptors is unchanged during acute changes in junctional NE concentrations.

Original languageEnglish
Pages (from-to)887-897
Number of pages11
JournalCirculation Research
Volume69
Issue number4
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • Adrenoceptors
  • Epinephrine
  • Methoxamine
  • Nitroprusside
  • Norepinephrine
  • Propranolol
  • Sympathetic nervous system
  • Trimethaphan
  • Yohimbine

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