Accentuation of ANP secretion to endothelin-1 in hypertrophied atria

To investigate modulation of ANP secretion by atrial hypertrophy, the secre tion of ANP in response to stretch and endothelin-1 was studied using isola ted perfused quiescent atria from rats treated with monocrotaline (MCT). Ma le Sprague-Dawley rats were given a single subcutaneous injection of 50 mg/ kg MCT or saline and were sacrificed at 6 weeks. Rats with right heart hype rtrophy showed an increase in ANP mRNA and decrease in tissue concentration of ANP in hypertrophied atria and a marked increase in plasma concentratio n of ANP. In isolated perfused hypertrophied right atria from MCT rats, cha nges in atrial volume induced by increased atrial pressure caused proportio nal increases in mechanically stimulated extracellular fluid (ECF) transloc ation and stretch-activated ANP secretion. Changes in atrial volume and mec hanically stimulated ECF translocation in hypertrophied right atria were no t different from those in control right atria. The stretch-activated ANP se cretion was suppressed without significant difference in basal ANP secretio n, as compared to control right atria. Therefore, the stretch-activated ANP secretion from hypertrophied right atria into the atrial lumen in relation to the ECF translocation (ANP concentration in the interstitium) was lower than that from control atria. A positive correlation between the stretch-a ctivated ANP secretion in relation to the ECF translocation and tissue ANP content was found in control atria but not in hypertrophied atria. Endothel in-1 caused increases in stretch-activated ANP secretion in a dose-dependen t manner, which were accentuated in hypertrophied right atria. Therefore, w e suggest that atrial hypertrophy causes an attenuated response to stretch and accentuated response to endothelin-1 of ANP secretion. (C) 2001 Elsevie r Science B.V. All rights reserved.