The sympathomimetic actions of l-ephedrine and d-pseudoephedrine: direct receptor activation or norepinephrine release?
The basic mechanisms by which ephedrine is preferred over other vasopressors in obstetric anesthesia have not been clearly defined. We examined the sympathomimetic effects of l-ephedrine, currently used as a vasopressor, and d-pseudoephedrine, currently used as a decongestant. In anesthetized rats, l-ephedrine and d-pseudoephedrine caused dose-dependent increases in arterial blood pressure and heart rate, and these effects disappeared after destruction of the sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA) pretreatment. The two ephedrine isomers produced concentration-dependent increases in tension of anococcygeal muscle and sinus rate of right atrium from rats. However, the anococcygeal and atrial responses to d-pseudoephedrine were abolished after 6-OHDA pretreatment, whereas approximately 50% of the responses to l-ephedrine were 6-OHDA-resistant. In human umbilical artery and vein, the two isomers failed to generate any contraction when given at the concentration that is capable of producing significant effects on anococcygeal and atrial tissues. Although direct adrenoceptor activation with l-ephedrine was detectable at tissue levels, the pressor response in vivo was entirely attributable to norepinephrine release from sympathetic nerves. This indirect mechanism could partly explain why l-ephedrine is better at increasing maternal arterial blood pressure while preserving the uteroplacental blood flow that is devoid of the involvement of the sympathetic innervation.


CONCLUSIONS
The indirectly sympathomimetic property of l-ephedrine may be one of the mechanisms to explain why ephedrine is preferred over alpha-adrenergic agonists as a vasopressor for treatment of intraspinal anesthesia-induced hypotension in obstetrics.
From the Departments of *Anesthesiology & Critical Care Medicine and †Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan; and the ‡Department of Anesthesiology, Yokohama City University School of Medicine, Yokohama, Japan.
Shigeaki
S
Kobayashi
Masayuki
M
Endou
Fumika
F
Sakuraya
Naoyuki
N
Matsuda
Xiao-Hong
XH
Zhang
Mitsue
M
Azuma
Noriyuki
N
Echigo
Osamu
O
Kemmotsu
Yuichi
Y
Hattori
Satoshi
S
Gando
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004809:Ephedrine / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000187:drug effects*; D013237:Stereoisomerism; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology*; D014469:Umbilical Arteries / Q000187:drug effects; D014471:Umbilical Veins / Q000187:drug effects
D011941:Receptors, Adrenergic; D013565:Sympatholytics; D013566:Sympathomimetics; D016627:Oxidopamine; D004809:Ephedrine; D009638:Norepinephrine