BNP GENE-EXPRESSION IS SPECIFICALLY MODULATED BY STRETCH AND ET-1 IN A NEW MODEL OF ISOLATED RAT ATRIA

We have assessed the effects of stretch or endothelin-1 (ET-1) on atri al natriuretic factor (ANF) and brain natriuretic peptide (BNP) secret ion 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 atri um. Stretch and ET-1 resulted in a transient stimulation of ANF and BN P secretion, with an initially larger proportional increase in ANF rel ease. Stretch and ET-1 induced a marked increase in BNP gene expressio n 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 a lso stimulated c-myc and Egr-1 mRNA levels, two markers of mechanical and receptor-mediated transcriptional activation. The selective respon se of the BNP gene to stretch and ET-1 and the distinct responses of A NF and BNP secretion indicate that the atrial cardiocytes have the cap ability to individually regulate the synthesis of its endocrine produc ts. This suggests that each hormone plays a specific role in the respo nse of the heart to hemodynamic or neuroendocrine imbalances.