Investigation of erythropoietin induced hypertension with special reference to nitric oxide

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Since the introduction of recombinant human erythropoietin to renal anemia, the development or aggravation of hypertension remains one of the most common and serious complications of this therapy. The precise mechanism in the development of hypertension are still not clear. Previous studies suggested that one of the major causes may be the increase of periphral vascular resistance, which derived from the increase of blood viscosity, endothelin, autonomic nervous system, peripheral oxygen tension and vascular endothelial dysfunction. It is also suggested that genetic predisposition to hypertension may relate to the etiology of erythropoietin induced hypertension. However, no conclusive results were so far obtained to explain for this type of hypertension.Recentrly, Caravaca et al reported anti-platelet aggregation drugs such as ditazole, ticlopidine, dipyridamole and aspirin prevented the development of hypertension treated with erytropoetin in retrospective study. They also observed in … More prospective study that antiplatelet drugs reduced blood pressure and periphral vascular resistance increased by erythropoietin treatment. They did not mention about the mechanism for this effect of antiplatelet aggregation drugs.In the present project, we observed antiplatelet drug, dipyridamole and ticlopidine, stimulated IL-1beta induced NO production in rat VSMC in culture. AS for dipyridamole, this compound enhanced the interleukin-1beta-induced NO production via inhibition of phosphodiesterase resulting in an increase of intracellular cAMP content in cultured rat vascular smooth muscle cells. On the other hand, ticlopidine enhanced the interleukin-1beta-induced NO production via stimulation of adenylate cyclase resulting in an increase of intracellular cAMP content.However, the clinical studies are needed to determine whether NO production could be stimulated by anti-platelet aggregation drugs, and whether the increased NO production might prevent erythropoietin induced hypertension in HD patients. Less