Direct evidence for erythropoietin-induced release of endothelin from peripheral vascular tissue.
The effect of recombinant human erythropoietin (r-HuEPO, 0.1 to 2.0 U/ml) on endothelin-1 (ET-1) release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal rats. r-HuEPO increased immunoreactive (ir-) ET-1 release in a dose-dependent fashion; the maximal percent increment in ir-ET-1 release evoked by r-HuEPO (2.0 U/ml) was about +210% over the basal rate of release. However, r-HuEPO showed no effect on release of angiotensin II, thromboxane B2 or vasodilatory prostaglandin I2 from the vasculature. These results not only provide direct evidence that r-HuEPO has the potential to specifically stimulate release of ET-1 from peripheral vascular beds, but, hence, suggest a contributory role of ET-1 in r-HuEPO-induced hypertension in anemic human subjects undergoing r-HuEPO therapy.
Katoh
K
K
Third Department of Internal Medicine, Fukushima Medical College, Japan.
Mizuno
K
K
Hashimoto
S
S
Okazaki
K
K
Asahi
K
K
Kuriki
M
M
Yamada
D
D
Fukuchi
S
S
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013929:Thromboxane B2 / Q000378:metabolism
D016232:Endothelins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000804:Angiotensin II; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000803:Angiotensin I