Nephrol Dial Transplant (2001) 16: 491-499
© 2001 European Renal Association-European Dialysis and Transplant Association
Erythropoietin modulates angiotensin II- or noradrenaline-induced Ca2+ mobilization in cultured rat vascular smooth-muscle cells
1 Departments of Nephrology and 2 Endocrinology and Metabolism, Jichi Medical School, Tochigi, Japan
Background. It has been reported that human recombinant erythropoietin (rHuEpo) modulates the sensitivity of the cardiovascular system to angiotensin II (Ang II) or noradrenaline (NA). In the present study, we explored the effect of rHuEpo on the responsiveness of Ang II- or NA-induced cytosolic free calcium ([Ca2+]i) mobilization in cultured rat vascular smooth-muscle cells (VSMC).
Methods. [Ca2+]i concentrations in VSMC were measured by using the calcium-sensitive fluorescent dye fura-2.
Results. The addition of rHuEpo (250 U/ml) alone induced elevation in [Ca2+]i, which remained significantly elevated above basal level for at least 60 min in the presence of extracellular Ca2+. Pre-incubation with specific protein kinase C (PKC) inhibitor calphostin C (1 µmol/l) significantly reduced the peak and the sustained elevations of [Ca2+]i. Pre-treatment with rHuEpo for 60 min increased both basal [Ca2+]i and the changes in [Ca2+]i by Ang II or NA in a dose-dependent manner in the presence of extracellular Ca2+. The synergistic effects of rHuEpo with Ang II or NA were also retained when VSMC were bathed in the Ca2+-free medium after the pre-incubation of rHuEpo. Conversely, they were diminished in the presence of extracellular Ca2+ combined with intracellular Ca2+ release inhibitor 8-(NN-diethylamino)octyl-1,3,4,5-trimethoxybenzoate (TMB-8). The synergistic effects of rHuEpo were also diminished by PKC depletion or by PKC inhibitor.
Conclusions. These observations suggest that rHuEpo has synergistic effects on Ang II- or NA-induced [Ca2+]i mobilization, particularly on intracellular Ca2+ release, in VSMC. This may be a potential mechanism contributing to hypertension associated with rHuEpo therapy.
Keywords: angiotensin II; cytosolic free Ca2+ mobilization; erythropoietin; noradrenaline; protein kinase C; vascular smooth-muscle cells
Correspondence and offprint requests to: Eiji Kusano MD, Department of Nephrology, Jichi Medical School, Yakushiji 3311-1, Minamikawachi, Tochigi 329-0498, Japan.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. E. Jie, M. C. Verhaar, M.-J. M. Cramer, K. van der Putten, C. A. J. M. Gaillard, P. A. Doevendans, H. A. Koomans, J. A. Joles, and B. Braam Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors Am J Physiol Renal Physiol, November 1, 2006; 291(5): F932 - F944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. R. Santhanam, L. A. Smith, K. A. Nath, and Z. S. Katusic In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase in cerebral arteries Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H781 - H786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Chu, Q. Tong, J. Y. Cheung, J. Wozney, K. Conrad, V. Mazack, W. Zhang, R. Stahl, D. L. Barber, and B. A. Miller Interaction of TRPC2 and TRPC6 in Erythropoietin Modulation of Calcium Influx J. Biol. Chem., March 12, 2004; 279(11): 10514 - 10522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J Smith, A. J Bleyer, W. C Little, and D. C Sane The cardiovascular effects of erythropoietin Cardiovasc Res, September 1, 2003; 59(3): 538 - 548. [Abstract] [Full Text] [PDF]
|
|