Hypertension induced by recombinant human erythropoietin (rHU-EPO) can be prevented by indomethacin. Pathogenetic role of cytosolic calcium.
Hypertension complicating the therapy of renal anemia with rHU-EPO is characterized by an increase in total peripheral vascular resistance, but the mechanisms underlying arteriolar vasoconstriction remain unclear. To assess the role of altered cellular calcium metabolism, resting platelet cytosolic calcium was measured in 12 previously normotensive patients with end-stage renal disease before and after 12 weeks of EPO-therapy, after 12 weeks of combined antihypertensive pharmacotherapy of EPO-induced hypertension, and after 12 weeks of concurrent administration of EPO and indomethacin. Patients with EPO-induced hypertension showed a significant raise in platelet calcium by comparison with calcium levels prior to EPO (179 +/- 15 vs 120 +/- 8 nmol/l), and there was a positive correlation between their blood pressure and platelet calcium levels (r = 0.9, p < 0.001). Antihypertensive therapy of EPO-induced hypertension resulted in a reduction of blood pressure and a reduction of platelet calcium to near normal levels (128 +/- 6 nmol/l). The non-steroidal antiinflammatory drug indomethacin prevented EPO-induced hypertension and EPO-associated alterations in platelet calcium. The results of the present study suggest that EPO-induced hypertension might be related to altered cellular calcium homeostasis. If EPO therapy induces alterations in calcium metabolism not only in platelets but also in vascular smooth muscle cells, these changes in calcium influx may contribute to arteriolar vasoconstriction during EPO therapy.
Schiffl
H
H
Medizinische Klinik, Klinikum Innenstadt der Universität München, Germany.
Lang
S M
SM
D000740:Anemia / Q000209:etiology / Q000628:therapy; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004921:Erythropoietin / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D007213:Indomethacin / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011994:Recombinant Proteins; D004921:Erythropoietin; D002118:Calcium; D007213:Indomethacin