It has been hypothesized that
autacoids, such as
endothelin-1 (ET), may modulate
erythropoietin (Epo) secretion. Therefore, we studied the effect of ET-1 infusion and of a nonselective ET(A/B) receptor antagonist on Epo secretion under
carbon monoxide (CO) exposure. Anesthetized rats were supplied with room temperature air containing increasing concentrations of CO by an aerating cap. A CO-Epo dose-response curve over the range of 0.02-0.14 vol% CO was conducted. Subpressor doses of ET-1 (3 pmol/min/kg BW) and the ET(A/B) receptor antagonist
LU302872 (LU; 30 mg/kg) were applied to anaesthetized rats under normoxia (controls
CON, ET, LU) and following
hypoxia (CO exposure; H-CON, H-ET, H-LU). Mean arterial blood pressure (MAP), glomerular filtration rate (GFR,
inulin clearance), Epo and ET-1 serum concentrations (ELISA) and renal Epo
mRNA (Light Cycler) were determined. The EC50 value for CO was 0.1 vol% with a 70-fold increase in Epo serum concentrations. CO exposure increased Epo serum and Epo
mRNA concentrations in the expected range in all groups. None of the treatments with ET or LU influenced the effect of
hypoxia on Epo serum concentrations and renal Epo
mRNA content. Under
hypoxia, administration of ET-1 as well as LU prevented the
hypoxia-induced decrease in MAP (p<0.05). Under
hypoxia, GFR was reduced by 50% except for H-LU with values comparable to normoxia. Taken together, the influence of
hypoxia exceeds by far the effect of ET-1 on Epo production, irrespective of the presence or absence of exogenous ET-1. Thus, ET-1 does not appear to be a major modulator of Epo production.