Potentiation of stretch-induced atrial natriuretic peptide secretion by intracellular acidosis

We sought to investigate whether atrial myocyte contraction and secretion o f the atrial natriuretic peptide (ANP) are affected in the same manner by i ntervention in intracellular Ca2+ handling by acidosis. The effects of prop ionate (20 mM)induced intracellular acidosis on the stretch-induced changes in ANP secretion, contraction force, and intracellular Ca2+ concentration ([Ca2+](i)) were studied in the isolated rat atrium. The stretch of the atr ium was produced by increasing the intra-atrial pressure of the paced and s uperfused preparation. Contraction force was estimated from pressure pulses generated by the contraction of the atrium. Intracellular Ca2+ was measure d from indo 1-AM-loaded atria, and ANP was measured by radioimmunoassay fro m the perfusate samples collected during interventions. Intracellular pH of the atrial myocytes was measured by a fluorescent indicator (BCECF)based i maging system. Intracellular acidification caused by 20 mM propionic acid ( 0.18 pH units) potentiated the stretch-induced (intra-atrial pressure from 1 to 4 mmHg) ANP secretion, causing a twofold secretion compared with nonac idotic controls. Simultaneously, the responsiveness of the atrial contracti on to stretch was reduced (P < 0.05, n = 7). Stretch augmented the systolic indo 1-AM transients in acidic (P < 0.05, n = 6) and nonacidic atria (P < 0.05, n = 6). However, during acidosis this was accompanied by an increase of the diastolic indo 1-AM ratio (P < 0.05, n = 6). Cooccurrence of stretch and acidosis caused an increase in systolic and diastolic [Ca2+](i) and po tentiated the stretch-induced ANP secretion, whereas the contraction force and its stretch sensitivity were decreased. This mechanism may be involved in ischemia-induced ANP secretion, suggesting a role for ANP secretion as a n indicator of contractile dysfunction.