In vivo studies on alpha-adrenergic receptor subtypes in human veins.
We studied in vivo responsiveness of venous alpha 1- and alpha 2-adrenoceptors, measuring the diameter changes in superficial veins in response to alpha-adrenergic agonists and antagonists in healthy human volunteers. The dorsal hand vein technique was used because it permits complete dose-response studies of venous constriction without confounding reflex alterations. Local infusions of all agonists studied induced dose-dependent contraction of the hand vein; the maximal effects (Emax) were: norepinephrine (88% +/- 10%), methoxamine (97% +/- 5%), phenylephrine (95% +/- 6%), clonidine 54% +/- 12%), and azepexole (68% +/- 26%). Clonidine reduced the norepinephrine-induced venoconstriction by 11% +/- 10%. Oral doses of 1 mg prazosin antagonized the venoconstriction induced by norepinephrine, methoxamine, and clonidine, but not by azepexole. Yohimbine-antagonism was observed against all agonists studied. Inhibition by yohimbine of clonidine-induced venoconstriction was irreversible over 60-180 min. Results show that the in vivo effects on veins of alpha-adrenergic agonists are in good agreement with results from in vitro experiments. Agonists with alpha 1- and alpha 2-adrenoceptor subtype selectivity cause venoconstriction in vivo, but alpha 2-receptor mediated constriction is intrinsically weaker. Clonidine acts as a partial antagonist against norepinephrine, presumably on postsynaptic alpha 2-receptors. At high doses, alpha 2-adrenoceptor subtype selectivity of clonidine and yohimbine appear to be partially lost in vivo.
Blöchl-Daum
B
B
1. Department of Medicine, Vienna University Hospital, Austria.
Korn
A
A
Wolzt
M
M
Schmidt
E
E
Eichler
H G
HG
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006225:Hand / Q000098:blood supply; D006801:Humans; D008297:Male; D011942:Receptors, Adrenergic, alpha / Q000145:classification* / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014680:Veins / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine