Increased production of erythropoietin after application of antidiuretic hormone. A consequence of renal vasoconstriction?
The renal glycoprotein hormone erythropoietin (Epo) is the key element in the feedback control of the production of red blood cells (RBC) in bone marrow. Excess of antidiuretic hormone (ADH) increases the RBC mass by increasing the synthesis of Epo. The mechanism of the Epo stimulating effect of ADH is not fully understood. Rats were treated with ADH with or without prior injection of a V1a-receptor antagonist. Additional experiments were carried out by stimulating the V2-receptor by desmopressin (DDAVP). Epo level in plasma was doubled following injections of ADH. Blockade of the V1a-receptor completely abolished the Epo stimulating effect of ADH. Neither ADH alone nor the combined giving of V1a-antagonist and ADH had an influence on the glomerular filtration rate or the renal plasma flow. Therefore, the increased Epo synthesis after application of ADH cannot be explained by a constriction of renal blood vessels with consecutive ischemic hypoxia. There is rather a direct stimulation of Epo synthesis by ADH via its receptors. Since a selective stimulation of the V2-receptor by DDAVP did not increase to Epo level in plasma, the observed increase of Epo is mediated by the V1a-receptor.
Institute of Physiology, Medical University, Lübeck, Germany.
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Engel
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Pagel
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001794:Blood Pressure / Q000187:drug effects; D004338:Drug Combinations; D004921:Erythropoietin / Q000096:biosynthesis* / Q000097:blood; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000502:physiology*; D014667:Vasopressins / Q000494:pharmacology*
D065092:Antidiuretic Hormone Receptor Antagonists; D004338:Drug Combinations; D017483:Receptors, Vasopressin; D014667:Vasopressins; D004921:Erythropoietin