Catecholamines, cardiac natriuretic peptides and chromogranin A: evolution and physiopathology of a ‘whip-brake’ system of the endocrine heart

In the past 50 years, extensive evidence has shown the ability of vertebrate cardiac non-neuronal cells to synthesize and releasecatecholamines (CA). This formed the mindset behind the search for the intrinsic endocrine heart properties, culminating in 1981with the discovery of the natriuretic peptides (NP). CA and NP, co-existing in the endocrine secretion granules and acting as majorcardiovascular regulators in health and disease, have become of great biomedical relevance for their potent diagnostic andtherapeutic use. The concept of the endocrine heart was later enriched by the identification of a growing number of cardiachormonal substances involved in organ modulation under normal and stress-induced conditions. Recently, chromogranin A(CgA), a major constituent of the secretory granules, and its derived cardio-suppressive and antiadrenergic peptides, vasostatin-1 and catestatin, were shown as new players in this framework, functioning as cardiac counter-regulators in ‘zero steady-stateerror’ homeostasis, particularly under intense excitatory stimuli, e.g. CA-induced myocardial stress. Here, we present evidence forthe hypothesis that is gaining support, particularly among human cardiologists. The actions of CA, NP and CgA, we argue, maybe viewed as a hallmark of the cardiac capacity to organize ‘whip-brake’ connection-integration processes in spatio-temporalnetworks. The involvement of the nitric oxide synthase (NOS)/nitric oxide (NO) system in this configuration is discussed. The useof fish and amphibian paradigms will illustrate the ways that incipient endocrine-humoral agents have evolved as components ofcardiac molecular loops and important intermediates during evolutionary transitions, or in a distinct phylogenetic lineage, orunder stress challenges. This may help to grasp the old evolutionary roots of these intracardiac endocrine/paracrine networksand how they have evolved from relatively less complicated designs. The latter can also be used as an intellectual tool todisentangle the experimental complexity of the mammalian and human endocrine hearts, suggesting future investigationalavenues.