Sensitization of human alpha 1- and alpha 2-adrenergic venous responses by guanadrel sulfate.
The alpha 1- and alpha 2-adrenergic venoconstriction in dorsal hand veins of normal subjects was determined by infusion of phenylephrine or clonidine. Oral administration of prazosin reduced the constriction response to phenylephrine but not to clonidine. Subjects were treated for 3 weeks in a randomized crossover design with placebo or guanadrel sulfate. Guanadrel reduced sympathetic tone (i.e., plasma norepinephrine and norepinephrine release rate), whereas venous responses to phenylephrine and clonidine were both augmented during guanadrel treatment. The effect on phenylephrine responses was primarily attributable to a decrease in the median effective concentration with a small increase in maximum response. Clonidine showed a markedly increased maximum response with a small increase in the median effective concentration. Platelet alpha 2-adrenergic receptors increased slightly but there was no change in the amount of platelet pertussis toxin substrate during guanadrel treatment. Thus reduction in sympathetic tone in normal young men results in increased venous responses to both alpha 1- and alpha 2-agonists.
Sekkarie
M A
MA
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0356.
Egan
B M
BM
Neubig
R R
RR
Supiano
M A
MA
D000293:Adolescent; D000328:Adult; D003000:Clonidine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006225:Hand / Q000098:blood supply; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood / Q000493:pharmacokinetics; D010656:Phenylephrine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D006146:Guanidines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; C004945:guanadrel; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin