[Effect of human recombinant erythropoietin (Epo) on cellular Ca2+, Na+, and K+ regulation of vascular smooth muscle cells grown in vitro--a new insight into the pathogenesis of Epo induced hypertension].
To gain an insight into the effect of erythropoietin (Epo) upon cation transporters and cytosolic free Ca2+ concentration ([Ca2+]i) of vascular smooth muscle cells (VSMC), we studied whether 1) Epo, per se, alters Ca2+ Na+, K+ fluxes and [Ca2+]i of VSMC, and 2) Epo may modify the effect of endothelin (ET-1). Using serially passaged quiescent cultured VSMC, the following results were obtained. 1) Epo had no direct effect on steady state Na(+)-K+ transporters (Na(+)-K+ pump, Na(+)-K+ cotransport and Na(+)-H+ antiport). 2) ET-1 alone substantially stimulated Na(+)-K+ pump, Na(+)-H+ antiport and 45Ca uptake, although these effects were not potentiated in the presence of Epo. 3) Epo alone substantially stimulated 45Ca uptake, leading to an increase in [Ca2+]i, which effect was not seen in Ca2+ deficient medium, and was partially inhibited with diltiazem but not with TMB-8. 4) Even in the presence of Epo, ET-1 and angiotensin II (A II) had substantial stimulatory effect on [Ca2+]i of cultured VSMC. The present data indicate that Epo, per se, elicits an increase in [Ca2+]i of VSMC through the stimulation of inward Ca2+ flux without affecting Na(+)-K+ transporters. In contrast, Epo did not potentiate ET-1's stimulatory effect on the transporters. Although the effect of Epo was subtle compared to ET-1 and A II, it may alter an overall characteristic of vascular smooth muscle cell contractility, possibly leading to blood pressure elevation in patients on maintenance dialysis.
Division of Nephrology, Saiseikai Central Hospital, Tokyo, Japan.
S
S
Kuriyama
G
G
Tokudome
H
H
Tomonari
H
H
Matsumoto
Y
Y
Utsunomiya
M
M
Horiguchi
H
H
Uchida
T
T
Hashimoto
O
O
Sakai
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*
D011994:Recombinant Proteins; D004921:Erythropoietin; D012964:Sodium; D011188:Potassium; D002118:Calcium