Stimulation of norepinephrine release by peripheral presynaptic beta-adrenoceptors.
Increases in plasma norepinephrine (NE) concentration induced by beta-agonist infusion have been taken as evidence for the existence of peripheral presynaptic beta-adrenoceptors, facilitating NE release. Concomitant hemodynamic changes, however, could invoke reflex mechanisms and thus hamper the interpretation of the results. We studied the presence of peripheral presynaptic beta-adrenoceptors by giving intra-arterial infusions of EPI in the forearm before and during uptake inhibition, and the effects of systemic infusions of very low-dose epinephrine (EPI) and isoproterenol (ISO) on hemodynamics and arterial and venous plasma NE concentrations. An i.a. infusion of EPI, 0.1 ng.kg-1.min-1, increased the net overflow of NE from 0.3 +/- 1.0 to 5.4 +/- 1.8 pmol.min-1 (M +/- SEM, p less than 0.05) and raised the calculated arterial plasma EPI concentration to 0.92 +/- 0.22 nmol.l-1. The uptake inhibition increased the net overflow of NE to 15.4 +/- 2.4 pmol.min-1 and during addition of EPI, 0.1 ng.kg-1.min-1, it further increased to 23.0 +/- 4.1 pmol.min-1 (p less than 0.05), while it decreased during addition of an effective beta-blocking dose of propranolol, 50 ng.kg-1.min-1 i.a., to 18.2 +/- 4.1 pmol.min-1 (n.s.). Systemic infusions of EPI and ISO increased blood pressure, heart rate, and forearm blood flow before significant changes in arterial or venous plasma NE concentrations were found. It is concluded that the increases in net NE overflow from the forearm during local EPI infusions indicate the presence of peripheral presynaptic beta-adrenoceptors which are responsive to physiologic concentrations of EPI. Systemic infusions of EPI or ISO elicit hemodynamic effects, and thus may invoke reflex mechanisms, before an influence on arterial or venous plasma NE concentration is found.
Chang
P C
PC
Department of Nephrology and Pharmacology, University of Leiden, The Netherlands.
Kriek
E
E
van der Krogt
J A
JA
Blauw
G J
GJ
van Brummelen
P
P
D000328:Adult; D004837:Epinephrine / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine