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 (AT1R). 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 < or = 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)] and returned to baseline after 24 hours (7.9 +/- 3.8 vs. 10.6 +/- 8.6 mU/mL, P = NS). With AT1R 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 AT1R.
RCT Entities:
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 (AT1R). 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 < or = 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)] and returned to baseline after 24 hours (7.9 +/- 3.8 vs. 10.6 +/- 8.6 mU/mL, P = NS). With AT1R 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 AT1R.
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