Pressor responses to ephedrine are mediated by a direct mechanism in the rat.
The mechanism of the pressor response to ephedrine is controversial. In the present study. i.v. injections of ephedrine increased systemic and pulmonary arterial pressure, and i.a. injections decreased hindlimb blood flow in a dose-related manner. Responses to ephedrine were inhibited by alpha-receptor blocking agents and were not attenuated by blockade of the norepinephrine reuptake transporter (NET) or by catecholamine depletion using reserpine or a combination of reserpine and alpha-methyl-p-tyrosine, whereas responses to tyramine and amphetamine were inhibited by these treatments. The magnitude of the pressor response to ephedrine was similar in anesthetized and conscious rats. Tachyphylaxis developed to pressor responses to ephedrine and amphetamine with sequential injections; however, ephedrine tachyphylaxis differed in that subsequent responses to alpha-receptor agonists were attenuated. These results suggest that the systemic and pulmonary pressor and hindlimb vasoconstrictor responses to ephedrine are mediated by direct action on alpha-adrenergic receptors and that the release of norepinephrine from adrenergic terminals plays no significant role. These results provide support for the hypothesis that responses to ephedrine are directly mediated in the intact rat, whereas responses to amphetamine are mediated in a large part by the release of norepinephrine from adrenergic terminals.
Liles
John T
JT
Department of Pharmacology SL83, School of Medicine, Tulane University Health Sciences Center, 1430 Tulane Ave., New Orleans, LA 70112, USA.
Dabisch
Paul A
PA
Hude
Keith E
KE
Pradhan
Leena
L
Varner
Kurt J
KJ
Porter
Johnny R
JR
Hicks
Alissa R
AR
Corll
Conni
C
Baber
Syed R
SR
Kadowitz
Philip J
PJ
D000661:Amphetamine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003042:Cocaine / Q000494:pharmacology; D004809:Ephedrine / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology
D002395:Catecholamines; D000697:Central Nervous System Stimulants; D011941:Receptors, Adrenergic; D010656:Phenylephrine; D012110:Reserpine; D000661:Amphetamine; D004809:Ephedrine; D003042:Cocaine; D009638:Norepinephrine