1. If one was to design a
hormone to protect the heart, it would have a number of features shown by the cardiac
natriuretic peptides atrial natriuretic peptide (
ANP) and
B-type natriuretic peptide (BNP). These
hormones are made in cardiomyocytes and are released into the circulation in response to atrial and ventricular stretch, respectively.
Atrial natriuretic peptide and BNP can reduce the preload and after-load in normal and failing hearts. They reduce blood volume over the short term by sequestering plasma and over the longer term by promoting renal
salt and water excretion and by antagonizing the renin-angiotensin-aldosterone system at many levels. Each of these actions affords indirect benefit to a volume- or pressure-threatened heart. 2. Recent studies have identified additional modes of action of the
natriuretic peptides that may also confer cardioprotective benefits, especially in
heart disease. The emerging findings are: (i) that
ANP and BNP antagonize the cardiac hypertrophic action of
angiotensin II and continue working under conditions where endothelial
nitric oxide (NO) function is compromised, such as in the presence of high
glucose in diabetes; (ii) they potentiate the
bradycardia caused by inhibitory ('autoprotective') cardio-cardiac reflexes; and, furthermore, (iii) BNP can suppress cardiac sympathetic nerve activity in humans, including those with
heart failure. Thus, it appears that
natriuretic peptides can shift sympathovagal balance in a beneficial direction (away from the sympathetic). The vagal reflex and antihypertrophic actions of the
peptides are mediated by particulate
guanylyl cyclase (pGC)
natriuretic peptide receptors. 3. The multiple synergistic actions of the
natriuretic peptides make them and their pGC receptors attractive targets for
therapy in
heart disease. Encouragingly, exogenous
natriuretic peptides remain effective even when endogenous
peptide levels are raised, as is the case in
heart failure. They also remain effective in disease states where other protective mechanisms, such as the NO system, have become ineffective, offering yet further encouragement for the
therapeutic use of the
natriuretic peptides.