Beta-adrenergic blockade decreases norepinephrine release in humans.
Beta-Adrenergic blockade with propranolol (PRP) has been reported to cause an increase in plasma norepinephrine (NE) levels in humans, which suggests that a reflex increase in sympathetic nervous system (SNS) vasoconstrictor tone compensates for the hypotensive effect of beta-adrenergic blockade. However, plasma NE levels are an indirect measure of SNS activity. We have developed a two-compartment model of NE kinetics to estimate NE release into an extravascular compartment as a more comprehensive measure of systemic SNS activity. To determine whether beta-adrenergic blockade alters extravascular NE release, we studied nine healthy subjects during sequential infusions of saline and PRP. During PRP infusion, there was an increase in plasma NE levels [1.03 +/- 0.13 to 1.27 +/- 0.21 (SE) nM; P = 0.05], but the extravascular NE release rate decreased significantly (15.5 +/- 1.6 to 9.2 +/- 1.2 nmol.min-1.m-2, P = 0.0002). The plasma NE concentration increased despite the fall in extravascular NE release rate primarily because the clearance of NE from plasma declined (1.55 +/- 0.08 to 1.18 +/- 0.07 l.min-1.m-2, P = 0.0001); the NE spillover rate into plasma did not change (1.73 +/- 0.18 to 1.75 +/- 0.23 nmol.min-1.m-2, P = 0.89). We conclude that PRP decreases extravascular NE release in humans. Suppression of SNS activity may be an additional mechanism of action of nonselective beta-adrenergic antagonists in humans.
Rosen
S G
SG
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Supiano
M A
MA
Perry
T J
TJ
Linares
O A
OA
Hogikyan
R V
RV
Smith
M J
MJ
Halter
J B
JB
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D009638:Norepinephrine / Q000097:blood*; D011433:Propranolol / Q000494:pharmacology*; D011865:Radioisotope Dilution Technique; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D012016:Reference Values; D014316:Tritium
D011943:Receptors, Adrenergic, beta; D014316:Tritium; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine