Vascular effects of pentoxifylline in humans.
In this study, we investigated the vasoactive effects of the alkylxanthine pentoxifylline and its interaction with the nucleoside adenosine in the forearm skeletal muscle vascular bed of 18 normotensive healthy volunteers. Pentoxifylline infusion into the brachial artery in dosages of 100, 300, and 1,000 micrograms/100 ml forearm volume (FAV)/min, induced increments of forearm blood flow (FBF) of 41 +/- 6, 125 +/- 22, and 295 +/- 57%, respectively (n = 12). Calculated forearm vascular resistance (FVR) showed a dose-dependent decrease during pentoxifylline infusion. Concomitant administration of caffeine (100 micrograms/100 ml/min), an adenosine antagonist, did not attenuate the vasodilator response to pentoxifylline (n = 6). Intraarterial (i.a.) infusion of adenosine alone (0.75, 1.5, 3.0, and 4.5 micrograms/100 ml/min) induced a dose-dependent forearm vasodilator response. Concomitant infusion of pentoxifylline (100 micrograms/100 ml/min) did not cause a convincing potentiation of the forearm vasodilator effect of adenosine. This study demonstrates that pentoxifylline induces vasodilation in human forearm skeletal muscle vascular bed of healthy young volunteers. This vasodilator response occurred at concentrations that are probably much higher than those achieved with oral treatment with pentoxifylline. Our data further suggest that pentoxifylline-induced vasodilation is not mediated by adenosine receptor stimulation, but may result from inhibition of the enzyme phosphodiesterase (PDE).
Kamphuis
J
J
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Smits
P
P
Thien
T
T
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000328:Adult; D002110:Caffeine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D018047:Receptors, Purinergic P1; D002110:Caffeine; D000241:Adenosine; D010431:Pentoxifylline