Increased vascular alpha1-adrenergic sensitivity in patients with renal failure: receiving recombinant erythropoeitin.
End stage renal disease (ESRD) is associated with altered hemodynamic regulation as a result of the pathophysiology or treatment of renal failure. Hypertension, common among dialysis patients, is a recognized complication of recombinant human erythropoietin (rHuEPO) therapy. We determined vascular adrenergic and nitric-oxide-mediated responsiveness in 7 patients with established ESRD on rHuEPO treatment and in 13 healthy volunteers using the dorsal hand vein technique. Sensitivity to the alpha1-adrenergic selective agonist phenylephrine was significantly increased in patients with ESRD on rHuEPO. The mean dose of phenylephrine producing 50% venoconstriction (ED50) was 38 +/- 1.6 ng/min in patients with ESRD and 135 +/- 1.3 ng/min in healthy volunteers-almost a 4-fold increase in dose, P = 0.01. In contrast, maximal venodilation mediated by bradykinin, an endothelium-dependent vasodilator, was not different in the 2 groups. To determine whether rHuEPO has a direct vasoconstrictor effect, we studied venous responsiveness to local infusions of rHuEPO in healthy volunteers. Increasing concentrations of rHuEPO produced no vasoconstriction in hand veins of healthy volunteers. These results suggest that vascular responsiveness to alpha-adrenergic stimulation in patients with ESRD on rHuEPO is increased whereas bradykinin-mediated venodilation remains intact. This increase in vascular alpha-adrenergic responsiveness may contribute to the increased peripheral vascular resistance and hypertension seen in patients with ESRD on rHuEPO.
Abiose
Ademola K
AK
Division of Cardiology, University of Iowa, Iowa City, IA; 2Division of Cardiology, New York Medical College, Valhalla, NY, USA.
Aronow
Wilbert S
WS
Moreno
Heitor
H
Nair
Chandra K
CK
Blaschke
Terrence F
TF
Hoffman
Brian B
BB
D000328:Adult; D001920:Bradykinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006225:Hand; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D011994:Recombinant Proteins; D006435:Renal Dialysis; D014655:Vascular Resistance / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014680:Veins / Q000187:drug effects / Q000473:pathology
D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D004921:Erythropoietin; D010656:Phenylephrine; D009569:Nitric Oxide; D001920:Bradykinin