Effects of uremic plasma on alpha- and beta-adrenoceptor subtypes.
Responsiveness of adrenergic receptors is decreased in patients on maintenance hemodialysis. In this study we investigated whether uremic plasma might affect adrenergic receptors. For this purpose we determined the effects of uremic plasma obtained from 10 patients on hemodialysis treatment (mean age 61 +/- 3 years, dialysis frequency 3 x 4 h/week, duration of treatment 3 +/- 1 years) before and at the end of the 4-hour dialysis treatment on binding of radioligands to beta1- and beta2- as well as alpha1- and alpha2-adrenoceptors. Plasma from 6 healthy volunteers served as control; the plasmas were studied in three dilutions: undiluted, 1:1 (v/v) and 1:4 (v/v) with saline diluted. Plasma from healthy control did not significantly affect the number of beta1- and beta2- or alpha1- and alpha2-adrenoceptors. On the other hand, uremic plasma significantly decreased the number of beta1- and beta2-adrenoceptors; this inhibitory effect was also observed when plasma obtained at the end of the 4-hour dialysis treatment was investigated. On the other hand, uremic plasma did not significantly decrease the number of alpha1- and alpha2-adrenoceptors. We conclude that in patients on maintenance hemodialysis, the presence of inhibitory substance(s) in uremic plasma could be - at least partly - responsible for the beta-adrenoceptor hyporesponsiveness; the mechanism leading ot alpha-adrenoceptor hyporesponsiveness, however, remains to be elucidated.
Ferchland
A
A
Institute of Pharmacology and Toxicology, Martin Luther University of Halle-Wittenberg, Halle, Germany.
Rettkowski
O
O
Pönicke
K
K
Deuber
H J
HJ
Osten
B
B
Brodde
O E
OE
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002585:Cesarean Section; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000628:therapy; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012016:Reference Values; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood*
D011942:Receptors, Adrenergic, alpha; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2