Losartan may modulate erythropoietin production

Abstract

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 blood flow 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 m 2 , RPF 650±29 ml/minute/1.73 m 2 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.

PlanHab: Hypoxia counteracts the erythropoietin suppression, but seems to exaggerate the plasma volume reduction induced by 3 weeks of bed rest

“…) that this central venous pressure increase is detected by the cardiac atrial volume receptors, which suppress EPO production, either by affecting the renin–angiotensin system (Freudenthaler et al. , ; Donnelly and Miller ), or via a humoral modulator stemming from the hypothalamic–hypophyseal system (Pagel et al. ; von Wussow et al.…”

“…During the early stages of bed rest, a thoraco-cephalad fluid shift prevails, resulting in a rapid and transient increase in central venous pressure (Nixon et al 1979;Linnarsson et al 1985). It has been postulated (Gunga et al 1996) that this central venous pressure increase is detected by the cardiac atrial volume receptors, which suppress EPO production, either by affecting the renin-angiotensin system (Freudenthaler et al 1999(Freudenthaler et al , 2000Donnelly and Miller 2001), or via a humoral modulator stemming from the hypothalamic-hypophyseal system (Pagel et al 1989;von Wussow et al 2005). In this regard, the report by Breymann et al (2000) showing that the increase in central venous pressure in a group of hypervolemic hemodiluted individuals was closely associated with a reduction in EPO is also of interest.…”

Renin-Aldosterone Paradox and Perturbed Blood Volume Regulation Underlying Postural Tachycardia Syndrome

“…First, in healthy subjects, infusions of angiotensin II caused serum erythropoietin levels to increase significantly, but this stimulation of erythropoietin was blocked when the subjects were premedicated with losartan, an angiotensin receptor blocker. 35,36 Second, plasma renin activity is higher among hemodialysis patients who do not require exogenous erythropoietin to maintain a hematocrit of 30% (which suggests adequate endogenous erythropoietin) than in those patients who require exogenous erythropoietin. 37 Third, plasma ultrafiltration induced a doubling of plasma renin activity, which was accompanied by a 69% rise in serum erythropoietin over 4 hours.…”

High cumulative incidence of cancer in patients with cardio‐renal‐anaemia syndrome

“…The most important stimulus for the production of EPO is renal hypoxia via hypoxia‐inducible factor (HIF)‐2α 8,9. Other important factors that influence the EPO levels are cytokines (IL‐1,TNF‐α)10 and the RAS 11–13. Despite high levels of EPO, patients with chronic HF and CKD are often anaemic.…”