Rg. Carlini et al., ENDOTHELIN-1 RELEASE BY ERYTHROPOIETIN INVOLVES CALCIUM SIGNALING IN ENDOTHELIAL-CELLS, Journal of cardiovascular pharmacology, 26(6), 1995, pp. 889-892
We investigated the effects of recombinant human erythropoietin (rHuEP
O) on intracellular calcium ([Ca2+](i)) and whether these changes regu
late both endothelin-l (ET-1) protein release and ET-1 messenger RNA (
mRNA) production in bovine pulmonary arterial endothelial cells (BPAEC
). rHuEPO (3.3 U/ml) induced [Ca2+](i) increases from a basal level of
54 +/- 12.2 (SE) to 147 +/- 21.1 nM (p < 0.001), in fura-2-loaded BPA
EC. In the presence of nifedipine (10 mu M), the increases in [Ca2+](i
) were significantly reduced. Furthermore, when extracellular calcium
([Ca2+](o)) was reduced (200 mu M), there was a significant reduction
in [Ca2+](i) increase after stimulation with rHuEPO. Incubation of BPA
EC with rHuEPO for 4 h increased ET-1 levels in the culture supernatan
t from 44.7 +/- 5.3 to 85 +/- 7.6 pg/ml (p < 0.001). However, when the
cells were treated with rHuEPO and nifedipine, the ET-1 levels were d
ecreased, as compared to levels resulting from treatment with rHuEPO a
lone (41 +/- 6.1 vs. 85 +/- 7.6 pg/ml, p < 0.001, respectively). rHuEP
O also induced a fourfold increase in the level of the preproET-1 mRNA
as compared with control. PreproET-1 mRNA was diminished in the prese
nce of nifedipine and rHuEPO and rHuEPO can increase [Ca2+](i) in BPAE
C, and this increase may be related to the stimulation of ET-1 synthes
is and release.