Pressor responses to ephedrine are not impaired in dopamine beta-hydroxylase knockout mice.
OBJECTIVE
Ephedrine and amphetamine can cause substantial increases in systemic arterial pressure. However, the role of endogenous noradrenaline release in mediating the pressor response to ephedrine is controversial. Studies using pharmacologic agents to decrease the synthesis, storage, and release of catecholamines have supported both a direct and an indirect mechanism of action for ephedrine. The purpose of the present study was to determine if endogenous noradrenaline release is required for cardiovascular responses to ephedrine and amphetamine using a genetic mouse model.


METHODS
Increases in systemic arterial pressure and heart rate in response to ephedrine and amphetamine were investigated and compared in dopamine beta-hydroxylase knockout (Dbh -/-) mice that cannot synthesize noradrenaline. Dbh +/- littermates have normal noradrenaline and adrenaline tissue levels, and served as controls in all experiments.


RESULTS
In Dbh -/- mice the increases in systemic arterial pressure and heart rate in response to i.v. injections of ephedrine were not impaired whereas responses to amphetamine were markedly reduced, when compared with responses in Dbh +/- mice. The pressor response to tyramine was abolished whereas pressor responses to noradrenaline, phenylephrine, dopamine, and angiotensin II were similar in Dbh -/- and Dbh +/- mice.


CONCLUSIONS
The present results in Dbh -/- mice provide support for the hypothesis that pressor responses to ephedrine are directly mediated whereas responses to amphetamine are dependent on the release of noradrenaline and suggest that Dbh +/- and Dbh -/- mice are useful for the study of direct and indirect mechanisms.
Liles
J T
JT
Department of Pharmacology, Tulane University Health Sciences Center, School of Medicine, Tulane University, New Orleans, LA 70112, USA.
Baber
S R
SR
Deng
W
W
Porter
J R
JR
Corll
C
C
Murthy
S N
SN
Thomas
S A
SA
Kadowitz
P J
PJ
D000818:Animals; D015153:Blotting, Western; D002395:Catecholamines / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D004809:Ephedrine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology
D002395:Catecholamines; D011433:Propranolol; D004299:Dopamine beta-Hydroxylase; D004809:Ephedrine; D014439:Tyramine; D010646:Phentolamine