Uraemia is necessary for erythropoietin-induced hypertension in rats.
1. There is no experimental proof that renal insufficiency is a necessary condition for hypertension during erythropoietin treatment. 2. The present study compares the effect of 3 weeks treatment with r-hu EPO (50 i.u./kg) on systolic blood pressure (SBP), haematocrit and plasma cGMP in an animal model of chronic renal failure (remnant kidney model excision) and sham-operated rats. 3. Sub-total nephrectomy induced a significant fall in haematocrit and a significant increase in plasma creatinine levels. Treatment with r-hu EPO resulted in a significant haematocrit increase in uraemic as well as in non-uraemic rats. Despite this effect, r-hu EPO treatment had no effect on SBP in sham-operated rats. On the contrary, this treatment caused significant SBP elevation in uraemic rats; in these rats, SBP increase did not correlate with haematocrit increase. 4. Plasma cGMP concentrations were significantly higher in uraemic compared to sham-operated rats and were not modified by r-hu EPO treatment. 5. This study provides evidence that renal insufficiency in rats is a prerequisite for the development of hypertension during erythropoietin treatment.
Poux
J M
JM
Département de Néphrologie (CHU Dupuytren), UFR de Pharmacie, Limoges, France.
Lartigue
M
M
Chaisemartin
R A
RA
Galen
F X
FX
Leroux-Robert
C
C
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003404:Creatinine / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects*; D006400:Hematocrit; D006973:Hypertension / Q000097:blood / Q000139:chemically induced* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D014511:Uremia / Q000097:blood / Q000150:complications*
D004921:Erythropoietin; D003404:Creatinine; D006152:Cyclic GMP