Losartan may modulate erythropoietin production.
Erythropoietin (Epo) is distinct amongst haematopoietic hormones, in that it is produced remote from the bone marrow. The tissue oxygen pressure required to trigger the Epo gene under physiological conditions is uniquely sited at a restricted area in the kidney termed the critmeter. Angiotensin II (Ang II) increases sodium reabsorption and hence oxygen consumption at any given bloodflow rate; therefore, it may affect the balance of renal oxygen supply vs. demand and hence Epo production. The purpose of this study was to determine whether Epo production is modulated by the renin-angiotensin system (RAS). Twenty normal subjects on a controlled sodium and protein diet had glomerular filtration rate (GFR) and renal plasma flow (RPF)assessed by standard methods of inulin and para-aminohippurate clearance, respectively, at baseline, hourly after the administration of losartan (25 mg) and after each 30 minute period of the infusion of Ang II at doses of 0.5, 1.5 and 2.5 ng/kg/minute. The baseline GFR was 115+/-4.0 ml/minute/1.73 m2, RPF 650+/-29 ml/minute/1.73 m2 and Epo 12.4+/-0.8 U/L. In spite of a marked increase in filtration fraction (FF) with Ang II, no changes in serum Epo levels were observed at two hours(11.7+/-1.3 U/L, p=n.s. compared with baseline). After the administration of losartan, there was a variable effect on FF, but a strong correlation of the change in serum Epo concentration and the change in FF(r=0.648, p=0.002), suggesting that the RAS may modulate Epo production.
Donnelly
S M
SM
St. Michael's Hospital, Toronto, Ontario, Canada. sandra.donnelly@utoronto.ca
Miller
J A
JA
D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004921:Erythropoietin / Q000096:biosynthesis*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D014662:Vasoconstrictor Agents; D004921:Erythropoietin; D000804:Angiotensin II; D012964:Sodium; D019808:Losartan