Catestatin is a novel endogenous peptide that regulates cardiac function and blood pressure

Catestatin is a 21-amino acid residue, cationic and hydrophobic peptide that is formed endogenously by proteolytic cleavage of its precursor chromogranin A, a major protein co-stored and co-released with catecholamines from the storage vesicles in adrenal chromaffin cells and adrenergic neurons. This peptide exhibits potent catecholamine release-inhibitory activity by acting on the neuronal nicotinic acetylcholine receptor. It also stimulates histamine release from mast cells via heterotrimeric G-proteins in a receptor-independent manner. Plasma levels of catestatin are diminished not only in hypertensive patients but also in their still-normotensive offspring, indicating its role in the pathogenesis of hypertension. Consistently, exogenous catestatin rescues hypertension in chromogranin A knockout mice and diminishes blood pressure responses to activation of sympathetic outflow in rats. These hypotensive actions of catestatin may be caused directly by autocrine inhibition of catecholamine release from the sympathoadrenal system and indirectly by paracrine stimulation of the potent vasodilator histamine release from mast cells. Recently, three human variants of catestatin displaying differential potencies for inhibition of catecholamine secretion have been identified. One of these variants (Gly364Ser) causes increased baroreceptor sensitivity, increased cardiac parasympathetic activity, and decreased cardiac sympathetic activity, and it seems to alter the risk for hypertension. These cardiovascular effects may have resulted by action of this peptide in the baroreceptor centre of the nucleus tractus solitarius. Thus, accumulating evidence documents the endogenous peptide catestatin as a novel regulator of cardiac function and blood pressure.