Plasma and blood vessel endothelin-1 concentrations in hypertensive uremic rats treated with erythropoietin.
The present study was designed to evaluate whether changes in plasma and blood vessel endothelin-1 (ET-1) concentrations may play a role in the enhanced blood pressure response to recombinant human erythropoietin (r-HuEPO) replacement therapy in uremia. Renal failure was induced by 5/6 nephrectomy (Nx). Uremic rats received either r-HuEPO (100 u s.c. three times a week) or the vehicle for 5 weeks. They were compared to control rats receiving the vehicle. Systolic blood pressure (tail cuff method), hematocrit, serum creatinine, plasma and tissue ET-1 were measured at the end of the protocol. Immunoreactive ET-1 (ir-ET-1) was determined by radioimmunoassay of acid-extracts from the plasma, thoracic aorta and mesenteric arterial bed. Creatinine increased about three fold in Nx animals. Blood pressure in control rats was 120+/-3 mmHg compared to 161 +/-6 mmHg in the Nx + vehicle group (p <0.01) and 199+/-9 mmHg in the Nx + r-HuEPO group (p <0.01 vs Nx + vehicle). Hematocrit in control rats was 41.3+/-0.4% vs 32.6+/-1.8% in the Nx + vehicle group (p <0.01) and 47.6+/-1.5% in the Nx + r-HuEPO group (p <0.01). Plasma ir-ET-1 levels were similar in the Nx + vehicle and Nx + r-HuEPO groups (7.9+/-1.0 and 7.8+/-0.8 pg/ml). In contrast, thoracic aorta ir-ET-1 content was significantly higher in the Nx + r-HuEPO group than in the Nx + vehicle group (20.3+/-2.9 vs 13.4+/-1.9 pg, p <0.05). Similar results were obtained in the mesenteric arterial bed. There were significant correlations between blood pressure and ir-ET-1 content in the thoracic aorta (r= 0.45, p<0.05) and in the mesenteric arterial bed (r= 0.41, p<0.05). Vascular ET-1 content but not plasma levels are increased in uremic rats treated with r-HuEPO suggesting an increase in blood vessel ET-1 production which may play a role in the pathogenesis of r-HuEPO-induced hypertension.
Lebel
M
M
CHUQ, L'Hôtel-Dieu de Québec Hospital, and Department of Medicine, Laval University, P.Q., Canada.
Lacasse-M
S
S
Larivière
R
R
Kingma
I
I
Grose
J H
JH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D004921:Erythropoietin / Q000627:therapeutic use*; D006400:Hematocrit; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D014511:Uremia / Q000097:blood / Q000378:metabolism*
D019332:Endothelin-1; D011994:Recombinant Proteins; D004921:Erythropoietin; D003404:Creatinine