Cardiac growth and contractility is profoundly altered in response to various
hormones and
neurotransmitters as well as by changes in electrolyte balance, blood volume, and blood pressure. In turn, the endocrine heart contributes to body homeostasis by secreting a number of biologically active
peptide hormones that act on several target tissues.
Atrial natriuretic peptide (
ANP) and B-type natiuretic
peptide (BNP) are the major secretory products of the endocrine myocardium. These
peptide hormones act on many target organs via
guanylate cyclase-linked membrane receptors to produce natriuresis, diuresis, vasodilatation, and
hypotension.
ANP and
BNP receptors are found on most organs involved in cardiovascular homeostasis (e.g., kidney, adrenal, vasculature, brain). They are also present in gonads and in pituitary, where they alter steroidogenesis and pituitary
hormone secretion. Not surprisingly, changes in blood pressure, volume, or
hormone status influence
ANP and BNP expression, which is also altered in almost all diseases that affect cardiac function. Thus, studies of
ANP and BNP gene expression are relevant for many clinical settings. Moreover, transcription of the
ANP and BNP genes characterizes cardiac cells at very early stages of development and is tightly linked to cardiac growth--be it proliferation, as in the fetal heart, or trophic growth, as in postnatal ventricular
hypertrophy. Thus, analysis of the molecular circuitry that controls
ANP and BNP expression might shed important insight into the complex regulatory pathways that underlie normal and pathologic heart development. Indeed, over the past few years, we have analysed transcriptional control of the
ANP and BNP genes in embryonic and postnatal cardiomyocytes and in cardiomyocytes treated with
hormones and
neurotransmitters that cause cardiomyocyte
hypertrophy. These studies have lead to the identification of distinct cis-acting
DNA elements that modulate basal and
hormone-stimulated transcription. Most importantly, the work also resulted in the isolation and characterization of cardiac-specific
transcription factors that play critical roles for cardiac cell differentiation and survival.