Cardiac Actions of Atrial Natriuretic Peptide

Chronic heart failure (HF) is a leading cause of morbidity and mortality worldwide. One important cause of HF is persistant arterial hypertension. Given the poor clinical prognosis, understanding the mechanisms preventing or driving hypertensive cardiac hypertrophy and the transition to failure is a major focus of research in cardiovascular medicine. In this issue, Perera et al1 provide new evidence for the existence of a protecting regulatory circuit in the heart, which involves the cardiac hormone atrial natriuretic peptide (ANP), its second messenger cyclic GMP (cGMP), and cGMP/cAMP cross-talk in cardiomyocytes. Forster resonance energy transfer (FRET) was used to monitor cAMP levels in specific submembrane microdomains of living myocytes under real-time conditions. The authors demonstrate that early hypertensive cardiomyocyte hypertrophy is accompanied by favorable spacial redistributions of the cGMP-modulated cAMP-hydrolyzing phosphodiesterase 2 (PDE2) and PDE3A between the microdomains of the β1- and β2-adrenergic receptors (AR). This molecular reorganization leads to ANP-induced augmentation of β1-AR stimulation of cAMP formation, and contractility, a circuit which may help to maintain contractile functions in early stages of heart hypertrophy.1Article, see p 1304 Since the original discovery that the hormones ANP and B-type natriuretic peptide (BNP) establish an endocrine axis between the heart and the kidneys,2,3 many additional physiological functions have been characterized. Via these hormones, the heart acts as networker between organs involved in the maintenance of blood pressure and metabolism. Physiologically, both NPs are mainly secreted from atrial granules into the circulation in response to acute or chronic atrial stretch.4 Their shared cGMP-producing guanylyl cyclase A (GC-A) receptor then mediates coordinated effects in the kidney, vasculature, adrenals, and central nervous system, which altogether are critical for the resetting of arterial blood pressure and intravascular volume homeostasis (Figure).4,5 …