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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.
S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
July 2009,
Acta physiologica (Oxford, England),
S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
February 1984,
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S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
June 1991,
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S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
July 1989,
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S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
July 1993,
Clinical pharmacology and therapeutics,
S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
October 2012,
Brain, behavior, and immunity,
S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
September 1967,
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S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
September 1982,
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S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
June 1976,
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S G Rosen, and
M A Supiano, and
T J Perry, and
O A Linares, and
R V Hogikyan, and
M J Smith, and
J B Halter
October 1986,
Journal of endocrinological investigation,
