Bianciotti, Liliana G., and Adolfo J. de Bold. Natriuretic peptide gene expression in DOCA-salt hypertension after blockade of type B endothelin receptor. Am J Physiol Heart Circ Physiol 282: H1127-H1134, 2002; 10.1152/ ajpheart.00468.2001.-We investigated the effect of longterm in vivo blockade of the ET-1 receptor subtype B (ET B) with A-192621, a selective ET B antagonist, on atrial and ventricular natriuretic peptide (NP) gene expression in deoxycorticosterone acetate (DOCA)-salt hypertension. In this model, stimulation of the cardiac natriuretic peptide (NP) and the endothelin system and suppression of the reninangiotensin system is observed. DOCA-salt induced significant hypertension, cardiac hypertrophy and increased NP plasma and left atrial and right and left ventricular NP gene expression. ET B blockade per se produced hypertension and left ventricular hypertrophy but induced little change on the levels of ventricular NP and only increased left atrial natriuretic factor (ANF) mRNA levels. Combined ET B blockade/ DOCA-salt treatment worsened hypertension, increased left ventricular hypertrophy and induced right ventricular hypertrophy. All animals so treated had increased ventricular NP gene expression. Collagen III and -myosin heavy chain gene expression were enhanced in both the right and the left ventricle of DOCA-salt hypertensive rats. The results of this study suggest that the ET B receptor does not participate directly in the modulation of atrial or ventricular NP gene expression and that this receptor mediates a protective cardiovascular function. ET B blockade can induce significant ventricular hypertrophy without an increase in ANF or brain NP gene expression. deoxycorticosterone acetate THE LEVEL OF EXPRESSION OF the cardiac natriuretic peptides (NP), atrial natriuretic factor (ANF), and brain natriuretic peptide (BNP), as well as circulating plasma levels, is increased by hemodynamic overload through mechanisms that are believed to involve both mechanical and neuroendocrine stimuli (7). The activation of the cardiac NP system serves to counterbalance the activity of systems that tend to increase extracellular fluid volume and blood pressure such as the renin-angiotensin-aldosterone and sympathetic systems (6). Although much information has been gathered regarding the regulation of NP gene expression and release through in vitro approaches, comparatively little is known regarding the long-term regulation of NP in the heart. Using a model of renovascular hypertension in the rat, we have previously found that there are two components that contribute to chronic increased NP gene expression. One component is independent of load and is concurrent with the hypertrophic process of chronically overloaded hearts whereas the other is dependent on hemodynamic load (26). We also reported that the expression of ANF and BNP in the ventricles and atria is differentially regulated. That is, in the atria, NP expression appears to be governed by mechanical stimuli (atrial muscle stretch) whereas in the ventr...