Recombinant erythropoietin increases blood pressure in experimental hypertension and uraemia without change in vascular cytosolic calcium

• Published in: Nephron (2015) Vol. 73; no. 2; p. 212
• Main Authors: Roger, S D, Fluck, R J, McMahon, A C, Raine, A E
• Format: Journal Article
• Language: English
• Published: Switzerland 1996
• Subjects: Analysis of Variance; Animals; Aorta, Thoracic - cytology; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Blood Pressure - drug effects; Calcium - metabolism; Creatinine - blood; Cytosol - metabolism; Erythropoietin - pharmacology; Hemoglobins - metabolism; Hypertension - genetics; Hypertension - physiopathology; In Vitro Techniques; Male; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Nephrectomy; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Recombinant Proteins; Urea - blood; Uremia - metabolism; Uremia - physiopathology
• ISSN: 1660-8151
• DOI: 10.1159/000189043

The mechanism of erythropoietin-induced hypertension in dialysis patients is unclear. Intracellular calcium ([Ca2+]i) may be altered in both hypertension and uraemia, and the effects of both uraemia and r-HuEPO on vascular smooth muscle [Ca2+]i and blood pressure (BP) in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were therefore studied. Male WKY and SHR underwent partial nephrectomy or sham operation. Three weeks later a 28-day period of treatment with either r-HuEPO 100 U/kg, s.c., 3 times/week or buffer was commenced (n = 10-12 for each subgroup). BP was measured weekly, by noninvasive Doppler tail-cuff assessment. [Ca2+]i was measured following loading with fura-2 in pooled, primary aortic vascular smooth muscle cells (VSMC). Serum urea and creatinine rose 3- to 4-fold after partial nephrectomy. Treatment with r-HuEPO did not change renal function further in either uraemic or control WKY or SHR. Haemoglobin increased in both non-uraemic WKY (16.2-20.3 g/dl) and SHR (16.4-20.5 g/dl) and uraemic animals (WKY 13.9-20.9; SHR 13.8-18.8 g/dl; p < 0.01 for all changes) following 4 weeks of r-HuEPO treatment. BP was unaffected by r-HuEPO in WKY but increased in nonuraemic SHR (210-250; p < 0.01) and in uraemic SHR (224-251 mm Hg; p < 0.001) at 4 weeks. VSMC [Ca2+]i was higher in SHR than WKY (121 vs. 83 nmol/l; MANOVA p < 0.05) but no effect of uraemia or r-HuEPO on [Ca2+]i was detected. In conclusion, the hypertensive effects of r-HuEPO are augmented both in a genetic model of hypertension and in uraemia. Although VSMC [Ca2+]i was elevated in SHR, the further increase in BP induced by r-HuEPO was not associated with alterations in VSMC cytosolic calcium.