Dilatory effects of phosphodiesterase inhibitors on human hand veins in vivo.
OBJECTIVE
To compare the venodilator potencies of the phosphodiesterase (PDE) III inhibitors amrinone and enoximone with the unspecific PDE inhibitors theophylline and pentoxifylline in human hand veins in vivo.


METHODS
Eighteen healthy nonsmokers (16 men and two women) were studied using the dorsal hand vein technique. After preconstriction with the selective alpha1-adrenergic-receptor agonist phenylephrine dose-response curves were constructed for amrinone (1-270 microg x min(-1)), enoximone (1-270 microg x min(-1)), theophylline (5-1500 microg x min(-1)) and pentoxifylline (2-877 microg x min(-1)) in a random order on separate occasions. Due to limitation in the maximum dose infused in order to avoid systemic effects, full dose-response curves could not be constructed for pentoxifylline. In this case, the individual dose of pentoxifylline and theophylline producing 50% venodilation were compared.


RESULTS
All PDE inhibitors induced dose-dependent venodilation. The value of maximum venodilation was the same for amrinone, enoximone and theophylline. The infusion rate needed to induce 50% of maximum venodilation (ED50) was not significantly different for amrinone (geometric mean, 8.8 microg x min(-1)) and enoximone (14.2 microg x min(-1)), whereas the ED50 of theophylline (84.0 microg x min(-1)) was significantly higher than either amrinone or enoximone. The dose necessary to dilate the vein to 50% the maximum dilation (as determined during sodium chloride infusion) was significantly higher for pentoxifylline than for theophylline (409 vs 71 microg x min(-1)).


CONCLUSIONS
These findings demonstrate that enoximone and amrinone have similar venodilatory potency which is six times higher than that of theophylline. The least potent vasodilator in this study was pentoxifylline.
Grossmann
M
M
Institute of Clinical Pharmacology, Faculty of Medicine, Technical University, Dresden, Germany. mgrossma@rcs.urz.tu-dresden.de
Braune
J
J
Ebert
U
U
Kirch
W
W
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000328:Adult; D000676:Amrinone / Q000494:pharmacology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004305:Dose-Response Relationship, Drug; D017335:Enoximone / Q000494:pharmacology; D005260:Female; D006225:Hand / Q000098:blood supply; D006801:Humans; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013806:Theophylline / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects* / Q000502:physiology
D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D013806:Theophylline; D017335:Enoximone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000676:Amrinone; D010431:Pentoxifylline