Natriuretic Peptides in the Central Nervous System

S. CAVALLERO; M.R. CHOI; A.M. PUYÓ; B.E. FERNÁNDEZ

Function of Neuropeptides at Central Nervous System

Research Signpost

Lugar: Kerala; Año: 2009; p. 119 - 148

The natriuretic peptide family is a group of structurally related peptides that exert diverse actions on cardiovascular, renal and endocrine functions. The major members of this family are atrial natriuretic peptide (ANP), brain or B-type (BNP) and C-type natriuretic peptide (CNP). They share a 17-amino acid disulfide ring structure with a highly conserved sequence. Their biological effects are elicited by binding to natriuretic peptide receptors NPR-A and NPR-B with subsequent activation of a catalytic domain with guanylate cyclase activity and generation of cyclic GMP. NPR-C is mainly considered a clearance receptor but it mediates some biological effects through activation of phospholipase C and inhibition of adenylate cyclase. Natriuretic peptides behave as physiological antagonists of the renin angiotensin system. Both cardiac and extracardiac natriuretic peptides constitute a vasodepressor system to counteract hypertensive and volume-overload situations. They increase diuresis and natriuresis, produce vasodilation by vascular smooth muscle relaxation, increase vascular permeability, thus facilitating plasma movement from capillaries to interstitial tissue and decrease sensitivity of the baroreflex system, lowering blood pressure. All these actions are coordinated by the brain natriuretic peptides system in order to maintain body fluid homeostasis.  ANP, BNP and CNP and their receptors are synthesized in several regions of the mammalian brain, particularly in those areas involved in the regulation of cardiovascular and renal functions and hydromineral homeostasis, like the anteroventral third ventricle area, the circumventricular organs and several hypothalamic nuclei. They are detected from the forebrain to the midbrain, including the telencephalon, diencephalon, metencephalon, mielencephalon and also the spinal cord. Several nuclei of the forebrain and the midbrain constitute a neural circuit involved in blood pressure regulation, water and electrolytes homeostasis, secretion of hypophyseal hormones and modulation of the peripheral sympathetic activity. These areas receive afferent inputs from peripheral arterial and cardiac baroreceptors, chemoreceptors and somatic receptors. In turn, they integrate the whole information and project efferent fibers from the brain to the sympathetic preganglionic neurons in the intermediolateral column of the spinal cord, thus modulating sympathetic activity. The neural circuit can be activated by changes in blood salt composition through the osmoreceptors located in the circumventricular organs or by angiotensin II or ANP, as well as by peripheral neural inputs that arrive to the nucleus tractus solitarii, via the activation of peripheral baroreceptors. From the nucleus tractus solitarii, second-order neurons project to the locus coeruleus and activate noradrenergic pathways which end in the median preoptic nucleus, paraventricular nucleus and supraoptic nucleus. These nuclei integrate the information showing the status of the hydromineral and pressure-volume homeostasis, and from there, noradrenergic neurons can modulate angiotensin II, ANP, arginine-vasopressin and oxytocin secretion. Natriuretic peptides inhibit aldosterone, vasopressin, corticotrophin releasing hormone and renin secretion. They also inhibit thirst and salt appetite. They decrease sympathetic activity through their inhibitory effects in noradrenergic neurotransmission, increasing uptake and endogenous content of norepinephrine in the central nervous system and decreasing its neuronal release. Natriuretic peptides and their receptors are involved in functional processes, like the central control of cardiovascular system, water and salt metabolism, neurohormones and hypophyseal hormones secretion, neurotransmitters release and uptake, angiogenesis, neural development, neural information processing and neuroprotection. BNP and CNP have a more widespread distribution in the brain, compared to that of ANP. The three peptides tend to be complementary, although there is some overlap of ANP with BNP and CNP.