AHEART July 46/1

Tavi, Pasi, Mika Laine, Sari Voutilainen, Petri Lehenkari, Olli Vuolteenaho, Heikki Ruskoaho, and Matti Weckström. Potentiation of stretch-induced atrial natriuretic peptide secretion by intracellular acidosis. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H405–H412, 1999.—We sought to investigate whether atrial myocyte contraction and secretion of the atrial natriuretic peptide (ANP) are affected in the same manner by intervention in intracellular Ca21 handling by acidosis. The effects of propionate (20 mM)induced intracellular acidosis on the stretch-induced changes in ANP secretion, contraction force, and intracellular Ca21 concentration ([Ca]i) were studied in the isolated rat atrium. The stretch of the atrium was produced by increasing the intra-atrial pressure of the paced and superfused preparation. Contraction force was estimated from pressure pulses generated by the contraction of the atrium. Intracellular Ca21 was measured from indo 1-AM-loaded atria, and ANP was measured by radioimmunoassay from the perfusate samples collected during interventions. Intracellular pH of the atrial myocytes was measured by a fluorescent indicator (BCECF)based imaging system. Intracellular acidification caused by 20 mM propionic acid (0.18 pH units) potentiated the stretchinduced (intra-atrial pressure from 1 to 4 mmHg) ANP secretion, causing a twofold secretion compared with nonacidotic controls. Simultaneously, the responsiveness of the atrial contraction to stretch was reduced (P , 0.05, n 5 7). Stretch augmented the systolic indo 1-AM transients in acidic (P , 0.05, n 5 6) and nonacidic atria (P , 0.05, n 5 6). However, during acidosis this was accompanied by an increase of the diastolic indo 1-AM ratio (P , 0.05, n 5 6). Cooccurrence of stretch and acidosis caused an increase in systolic and diastolic [Ca]i and potentiated the stretchinduced 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 an indicator of contractile dysfunction.