Increased endothelin: nitric oxide ratio is associated with erythropoietin-induced hypertension in hemodialysis patients.
Regular administration of recombinant human erythropoietin (rHuEPO) is frequently associated with a rise in arterial blood pressure in hemodialysis (HD) patients. The aim of this study was to examine the effects of rHuEPO on plasma endothelin (ET)-1 and nitric oxide products (NOx) concentration in HD patients. Fifteen patients on maintenance HD with hematocrit of less than 25% were included in the present study. All patients received 3,000 units of rHuEPO intravenously three times a week at the end of each HD session. Plasma levels of ET-1, NOx, thromboxane B2 (TXB2), prostacyclin (6-keto-PGF1alpha), and cyclic guanosine 3',5'-monophosphate (cGMP) were measured before, 2, and 4 weeks after rHuEPO treatment. Plasma concentrations of ET-1, TXB2, and 6-keto-PGF1alpha were measured by radioimmunoassay. Plasma NOx was measured by high-performance liquid chromatography. An rHuEPO-induced increase in mean arterial blood pressure of over 6 mmHg occurred in 7 patients (hypertensive group), whereas the elevation of mean arterial blood pressure was less than 5 mmHg in 8 patients (nonhypertensive group). Plasma ET-1 levels were elevated in all HD patients. Elevated plasma ET-1 levels remained unchanged after rHuEPO treatment in the hypertensive group, whereas the increase in plasma ET-1 levels was attenuated in the nonhypertensive group. Plasma NOx concentrations were also increased in all HD patients. This increase in plasma NOx levels was lessened in the hypertensive group after rHuEPO administration; however, plasma NOx levels remained increased in the nonhypertensive group. Changes in mean arterial blood pressure were significantly correlated with changes in plasma ET-1/NOx ratio. Plasma levels of TXB2, 6-keto-PGF1alpha, and cGMP were unchanged after rHuEPO administration in the hypertensive and nonhypertensive groups. These results suggest that an increase in ET-1/NOx ratio in blood, probably occurring in vascular endothelial cells, may be associated with rHuEPO-induced hypertension in HD patients.
Shimada
N
N
Division of Nephrology and Hypertension, Department of Medicine, Koto Hospital, Tokyo, Japan.
Saka
S
S
Sekizuka
K
K
Tanaka
A
A
Takahashi
Y
Y
Nakamura
T
T
Ebihara
I
I
Koide
H
H
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000097:blood; D019332:Endothelin-1 / Q000097:blood* / Q000187:drug effects; D004921:Erythropoietin / Q000009:adverse effects; D005260:Female; D006400:Hematocrit; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D007564:Japan; D007676:Kidney Failure, Chronic / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D011994:Recombinant Proteins; D006435:Renal Dialysis; D013223:Statistics as Topic; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D019332:Endothelin-1; D011994:Recombinant Proteins; D004921:Erythropoietin; D009569:Nitric Oxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D006152:Cyclic GMP