IntroductionWe previously demonstrated that brain natriuretic peptide (BNP) is a cardiac hormone mainly produced in the ventricle, while the major production site of atrial natriuretic peptide (ANP) is the atrium. 1. Abbreviations used in this paper: ANP, atrial natriuretic peptide; BNP, brain NP; ET-1, endothelin-1; HP-GPC, high performance gel permeation chromatography; -LI, like immunoreactivity; MLC-2, myosin light chain-2; PKC, protein kinase C.The identification of atrial natriuretic peptide (ANP)' in the cardiac atrium (1, 2) uncovered a new functional role of the heart as an endocrine organ regulating body fluid homeostasis and blood pressure control (3-5). ANP is mainly produced in and released from the atrium, and the plasma ANP concentration elevates in volume-overloaded states including congestive heart failure (6-8). In addition, the gene expression of ANP in the ventricle is markedly induced during the process of cardiac hypertrophy upon ventricular overload, and significantly contributes to the increase in the plasma ANP concentration in various cardiovascular disorders (9-11).Brain natriuretic peptide (BNP), originally isolated from the porcine brain (12), is a second member of natriuretic peptide family (3-5). We previously demonstrated that BNP is predominantly synthesized in and secreted from the cardiac ventricle (13-15). We have further shown that the ventricular gene expression of BNP is substantially augmented in response to ventricular overload in congestive heart failure, idiopathic cardiomyopathy, or hypertensive heart disease with cardiac hypertrophy (14-17). Although the plasma BNP concentration is approximately one-sixth of the plasma ANP concentration in healthy men, it markedly elevates in patients with congestive heart failure in parallel with its severity and surpasses the plasma ANP concentration in severe cases (14,(18)(19)(20). Furthermore, we have recently demonstrated that the plasma BNP concentration increases rapidly and tremendously, in contrast to the modest change of the plasma ANP concentration, in the early clinical course of acute myocardial infarction (21,22). These findings indicate that the biosynthesis and secretion of BNP are distinctly regulated from those of ANP in response to ventricular overload, and suggest that BNP may have a discrete pathophysiological role in the maintenance of cardiovascular homeostasis.The augmented productions of BNP and ANP in the hypertrophied myocardium can be considered as a compensation mechanism against ventricular overload, since BNP and ANP serve to reduce both cardiac preload and afterload by their natriuretic, diuretic, and vasodilatory actions (23)(24)(25). It will be of great importance to characterize the gene expressions of BNP and ANP during the development of cardiac hypertrophy, which also constitutes one of the principal adapting mechanisms against increased ventricular workload (26). The cellular mechanisms of the cardiac adaptations to ventricular overload, especially the expressions of various cardiac-spe...