The interplay between chromogranin A-derived peptides and cardiac natriuretic peptides in cardioprotection against catecholamine-evoked stress.

Chromogranin A (CgA) is the major soluble protein co-stored and co-released with catecholamines (CAs) from secretory vesicles in the adrenal medulla chromaffin cells. Present in the diffuse neuroendocrine system, it has also been detected in rat and human cardiac secretory granules where it co-stores with natriuretic peptide hormones (NPs). Mounting evidence shows that CgA is a marker of cardiovascular dysfunctions (essential hypertension, hypertrophic and dilatative cardiomyopathy, heart failure) and precursor of the cardioactive peptides vasostatin-1 (VS-1) and catestatin (Cts). This review focuses on recent knowledge regarding the myocardial, coronary and anti-adrenergic actions of VS-1. In particular, the negative inotropism, lusitropism and coronary dilation effects of rat CgA1-64 (rCgA) and human recombinant STACgA1-78 (hrSTACgA1-78) are summarized with attention on their counteracting isoproterenol- and endothelin-1-induced positive inotropism, as well as ET-1-dependent coronary constriction. The interactions between vasostatins (VSs), NPs and CA receptors are proposed as a paradigm of the heart capacity to organize complex connection-integration processes for maintaining homeostasis under intense cardio-excitatory stimuli (myocardial stress).