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 at rial myocytes, EPO is involved in the long-term defense mechanism agai nst hypoxia via stimulation of erythropoiesis. ANP is involved in the short-term defense mechanism against hypoxia via improved pulmonary an d heart functions, We investigated a possible interaction between thes e two hormones. We tested the hypothesis that EPO may stimulate ANP se cretion from the cardiac atrium. This hypothesis was tested in two in vitro models: isolated rat atrium and cultured adult atrial rat myocyt es. Recombinant human EPO (5-10 units/ml) enhanced ANP secretion from the isolated atrium (by similar to 2-fold) within 10 min in a concentr ation-dependent manner. To define whether the action of EPO on ANP sec retion is direct, we examined the effect of EPO on ANP release from ad ult rat cultured atrial myocytes. EPO failed to stimulate ANP secretio n from cultured atrial myocytes, suggesting that EPO-induced ANP secre tion is an indirect effect. Cyclooxygenase products (e.g., prostagland ins) and endothelin 1 were shown to be potent secretagogues of ANP fro m cardiac atrium. To test whether EPO-induced ANP secretion from isola ted perfused atrium is mediated by cyclooxygenase products and/or endo thelin, we used inhibitors of the enzyme cyclooxygenase (indomethacin or aspirin) and the endothelin receptor ET(A) 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 abolis hed EPO-stimulated ANP secretion from cardiac atrium. Our results expa nd our knowledge on the interaction between EPO and ANP hormonal syste ms and their possible role in the acute defense mechanism against hypo xia.