Influence of recombinant human erythropoietin on blood pressure and tissue renin-angiotensin systems.
In humans, blockade of the renin-angiotensin system with angiotensin converting-enzyme inhibitors (ANG CEI) prevents the rise in blood pressure associated with the administration of recombinant human erythropoietin (rhEPO). This study was conducted to determine whether rhEPO elevates blood pressure in normal Wistar rats and whether the renin-ANG system is affected. Groups of 10 rats each were given rhEPO, ANG CEI (enalapril), rhEPO + ANG CEI, or vehicle. Renin and/or renin substrate mRNA was measured in aortas, kidney, and heart; renin activity (PRA), inactive renin, and renin substrate were measured in plasma. rhEPO raised blood pressure in the normal rat without changing the plasma renin system. ANG CEI prevented this blood pressure rise. Renin-specific mRNA was increased by rhEPO in renal tissue, and renin substrate mRNA was significantly elevated in the kidney and aorta. mRNA for renin and renin substrate were not altered in the heart. In both aorta and kidney, a significant correlation was observed between renin substrate mRNA and blood pressure. The data indicate that rhEPO modulates specific tissue renin-ANG systems, which may contribute to blood pressure elevation.
Eggena
P
P
Veterans Administration Medical Center, Sepulveda, California 91343.
Willsey
P
P
Jamgotchian
N
N
Truckenbrod
L
L
Hu
M S
MS
Barrett
J D
JD
Eggena
M P
MP
Clegg
K
K
Nakhoul
F
F
Lee
D B
DB
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001769:Blood / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D004656:Enalapril / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000187:drug effects*
D011994:Recombinant Proteins; D004921:Erythropoietin; D004656:Enalapril; D012083:Renin