We have assessed the effects of stretch or endothelin-1 (ET-1) on atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) secretion and gene expression using a new model of isolated right atria from the rat. This model allows for comparatively long-term in vitro study of adult tissue while retaining the anatomic conformation of the atrium. Stretch and ET-1 resulted in a transient stimulation of ANF and BNP secretion, with an initially larger proportional increase in ANF release. Stretch and ET-1 induced a marked increase in BNP gene expression after 1.5 and 4 h, respectively; the increase in BNP mRNA levels was maintained throughout the 8-h experimental period. Stretch and ET-1 also stimulated c-myc and Egr-1 mRNA levels, two markers of mechanical and receptor-mediated transcriptional activation. The selective response of BNP gene to stretch and ET-1 and the distinct responses of ANF and BNP secretion indicate that the atrial cardiocytes have the capability to individually regulate the synthesis of its endocrine products. This suggests that each hormone plays a specific role in the response of the heart to hemodynamic or neuroendocrine imbalances.