Erythropoietin stimulates atrial natriuretic peptide secretion from adult rat cardiac atrium.
Hypoxia is a powerful stimulus for erythropoietin (EPO) secretion from the kidney and for atrial natriuretic peptide (ANP) secretion from atrial myocytes. EPO is involved in the long term defense mechanism against hypoxia via stimulation of erythropoiesis. ANP is involved in the short-term defense mechanism against hypoxia via improved pulmonary and heart functions. We investigated a possible interaction between these two hormones. We tested the hypothesis that EPO may stimulate ANP secretion from the cardiac atrium. This hypothesis was tested in two in vitro models; isolated rate atrium and cultured adult atria rat myocytes. Recombinant human EPO (5-10 units/ml) enhanced ANP secretion from the isolated atrium (by approximately 2-fold) within 10 min in a concentration-dependent manner. To define whether the action of EPO on ANP secretion is direct, we examined the effect of EPO on ANP release from adult rat cultured atrial myocytes. EPO failed to stimulate ANP secretion from cultured atrial myocytes, suggesting that EPO-induced ANP secretion is an indirect effect. Cyclooxygenase products (e.g.,prostaglandins) and endothelin 1 were shown to be potent secretagogues of ANP from cardiac atrium. To test whether EPO-induced ANP secretion from isolated perfused atrium is mediated by cyclooxygenase products and/or endothelin, we used inhibitors of the enzyme cyclooxygenase (indomethacin or aspirin) and the endothelin receptor ETA subtype antagonist BQ123. EPO-stimulated ANP secretion was not affected by indomethacin (10(-4) M) or aspirin (10(-4) M), whereas BQ123 (10(-6) M) completely abolished EPO-stimulated ANP secretion from cardiac atrium. Our results expand our knowledge on the interaction between EPO and ANP hormonal systems and the possible role in the acute defense mechanism against hypoxia.
Porat
O
O
Department of Physiology and Pharmacology, Tel Aviv University, Israel.
Neumann
D
D
Zamir
O
O
Nachshon
S
S
Feigin
E
E
Cohen
J
J
Zamir
N
N
D000818:Animals; D016275:Atrial Function / Q000187:drug effects*; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D008297:Male; D011460:Prostaglandins F / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D011460:Prostaglandins F; D004921:Erythropoietin; D009320:Atrial Natriuretic Factor