Angiotensin II infusion increases plasma erythropoietin levels via an angiotensin II type 1 receptor-dependent pathway

Background. Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to lower hematocrit and erythropoietin (EPO), but a direct link between angiotensin II (Ang II) and EPO in humans has not been shown. Methods. placebo or Ang II was infused for six hours in nine healthy male volunteers with and without blockade of the Ang II subtype 1 receptor (AT(1)R). EPO concentrations were measured 3, 6, 12, and 24 hours after the start of the infusion. Results. Ang II raised the mean arterial pressure by about 20 mm Hg. Consistent with the known diurnal variation, EPO levels rose significantly (P less than or equal to 0.02) during the day in all groups. During Ang II infusion, EPO levels rose to significantly higher levels after 6 and 12 hours compared with placebo [9.9 +/- 3.5 vs. 7.2 +/- 3.1 mU/mL (3 h, P = NS); 16.9 +/- 4.5 vs. 8.8 +/- 3.7 mU/mL (6 h, P = 0.01): 17.0 +/- 8.6 vs. 11.1 +/- 4.7 mU/mL (12 h, P = 0.01)1 and returned to baseline after 24 hours (7.9 +/- 3.8 vs. 10.6 +/- 8.6 mU/mL, P = NS). With AT(1)R blockade, blood pressure remained normal during Ang II infusion, and EPO levels were never significantly different from placebo [6.8 +/- 4.8, 10.5 +/- 5.6, 13.1 +/- 9.0, and 12.4 +/- 10.1 mU/mL at 3, 6, 12, and 24 h after infusion, respectively, P = NS]. Conclusions. Ang II increases EPO levels in humans. This increase requires the participation of AT,R.