Besides a blood pumping function, the mammalian heart is also known as an endocrine organ. Atrial natriuretic peptide (ANP) and brain or B-type natriuretic peptide (BNP) are members of the natriuretic hormone family released by cardiac cells (Ruskoaho 1992, Davidson & Struthers 1994). ANP is mainly produced by atrial myocytes while BNP is produced by both the atria and ventricles. Both peptides are involved in the regulation of blood pressure and fluid homeostasis (Wilkins et al. 1997, Levin et al. 1998). Atrial wall stretching is the predominant stimulus for the secretion of ANP (Lang et al. 1985, Ruskoaho 1992). Wall stretch appears also to be a potent stimulus for ventricular ANP release (Kinnunen et al 1992) and for the secretion of BNP from the ventricles (Kinnunen et al. 1993) and atria (Mäntymaa et al. 1993) in vitro. The primary sensors for stretch-dependent cardiac hormone secretion may be cardiac myocytes, but other cell types, including endothelial and endocardial cells may also be involved in the activation of cardiac hormone release.
A number of different cell types have transduction systems that convert externally applied mechanical forces to signals that regulate cellular function (Watson 1991). Cardiac myocytes have the ability to sense mechanical stretch and convert it into intracellular signals, which lead e.g. to hypertrophy (Sadoshima & Izumo 1997) or secretion of ANP from atrium (Lang et al. 1985, Ruskoaho 1992). Mechanical stretch rapidly activates multiple cellular signaling pathways in myocytes (Sadoshima & Izumo 1993a). These second messenger pathways include e.g. phospholipid system and protein kinase C (PKC) which are thought to be associated in ANP secretion from myocytes (Ruskoaho 1992). Although it is well known that mechanical forces have many effects on the structure and function of cells, little is known of how the mechanical stimuli are converted into intracellular signals and cardiac hormone secretion. The purpose of this study was to examine the mechanism regulating natriuretic peptide release, particularly those pathways that are involved in atrial wall stretch-induced natriuretic peptide exocytosis.