The Endocrine–Paracrine Control of the Cardiovascular System

Abstract

Over the last 50 years, a large number of cardiovascular studies have identified in vertebrates the ability of cardiac nonneuronal cells to synthesize and release catecholamines (CAs) and the natriuretic peptides (NPs). Thanks to compartmentalized cardiac and vascular receptors, these substances, through activation of local autocrine and paracrine circuits, regulate cardiovascular homeostasis in health and disease. In particular, biomedically oriented research has extensively analysed CAs and NPs in mammals, since these substances are regarded with interest in view of their potent diagnostic and therapeutic implications. This knowledge has firmly established the concept of the heart as an endocrine organ. Such a scenario was dramatically enriched by the identification of a growing number of molecules (i.e., angiotensin II, adrenomedullin, ghrelin, neuropeptide Y, etc.) which, produced by the heart, exert endocrine/paracrine/autocrine cardiac actions. More recently, chromogranin-A (CgA) and its derived cardio-suppressive and antiadrenergic peptides (vasostatin-1 and catestatin) have revealed themselves as new players in this framework, functioning as cardiac stabilizers, particularly in the presence of intense excitatory stimuli such as those acting under stress, including CA responses. The intracardiac nitric oxide synthase (NOS)/nitric oxide (NO) system works as a very sensitive autocrine/paracrine spatio-temporal organizer through connection–integration processes, playing a role in network configuration. This chapter comparatively summarizes the information available on the hearts of cold-blooded vertebrates with regard to these major endocrine and paracrine agents, although many serious gaps are particularly evident in amphibians and reptiles due to discontinuous information being available. Some paradigmatic examples will help the reader to grasp, with a historical approach, the ways in which incipient endocrine agents, with their molecular loops, have evolved as important cardiac modulators, and how they have become critical intermediates during evolutionary transitions or in a distinct phylogenetic lineage. At the same time, a better understanding of the old evolutionary roots of these networks, and how they have evolved from relatively less complicated designs, can help to disentangle the experimental complexity which characterizes the endocrine heart at higher organization levels.