Effect of endothelin-1 on erythropoietin production in a rat model under normoxia and functional carbon monoxide-induced hypoxia

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 w...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 2006-08, Vol.373 (5), p.342-348
Main Authors: Grenz, A, Klein, J, Köhle, C, Freudenthaler, S, Proksch, B, Wu, J, Wolf, S, Osswald, H, Gleiter, C H
Format: Article
Language:English
Subjects:
Animals
Blood Pressure
Carbon Monoxide - metabolism
Endothelin A Receptor Antagonists
Endothelin B Receptor Antagonists
Endothelin-1 - blood
Endothelin-1 - pharmacology
Endothelin-1 - physiology
Erythropoietin - biosynthesis
Erythropoietin - blood
Glomerular Filtration Rate
Hypoxia - metabolism
Kidney - metabolism
Male
Rats
Rats, Sprague-Dawley
RNA, Messenger - biosynthesis
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Summary: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
ISSN:0028-1298
1432-1912
DOI:10.1007/s00210-006-0085-y