The central effects of the natriuretic peptides are comparable to those in the periphery, i.e. augmentation of natriuresis and diuresis and modulation of salt and water homeostasis. Natriuretic peptides are specifically involved in the regulation of the hypothalamo-pituitary-adrenocortical (HPA) system: in man and rodents ANF inhibits the HPA system at all regulatory levels, while CNP stimulates the release of cortisol.
Angiotensin is the antagonistic counterpart of the natriuretic peptides with respect to central water and salt homeostasis. Intraventricular application of angiotensin, for example, induces thirst, whereas intraventricular application of natriuretic peptides suppresses thirst.
The central cardiovascular effects of the natiuretic peptides depend on their control of vasopressin secretion from the paraventricular and supraoptic nucleus of the hypothalamus.
In the periphery, angiotensin II and the natriuretic peptides also exhibit opposite effects. Most of the peripheral effects are related to fluid homeostasis of the organism. ANF enhances natriuresis and diuresis by regulating the filtration rate in the glomeruli and by increasing renal perfusion. In addition, ANF blocks the vasopressin-dependent reabsorption of Na+, resulting in an enhanced diuresis and natriuresis.
Besides its direct vasodilator action, ANF exerts indirect effects on the cardiovascular system by inhibiting the secretion of aldosteron and renin.
Since BNP shows co-secretion with ANF, it is believed that BNP cooperates with ANF in the regulation of blood pressure and in salt homeostasis. Consistent with this idea is the finding that hypertensive patients show an increase of both peptides under a low-Na+ diet.
In contrast to BNP and ANF, the C-type natriuretic peptide (CNP) has minor effects upon natriuresis and diuresis. CNP seems to possess an anti-proliferative action on smooth muscle cells in vitro and induces vasodilatation as well as relaxation of smooth muscle cells in the bronchi.
The natriuretic peptides are also thought to play a role in higher brain functions. In rodents, ANF was found to reduce anxiety levels, whereas CNP induced the opposite effect. In patients with panic disorder, basal ANF plasma levels are lower in comparison to healthy volunteers, but ANF secretion is faster and more pronounced during experimentally induced panic attacks. Interestingly, panic anxiety and concomitant ACTH and cortisol secretion elicited by stimulation with cholecystokinin tetrapeptide were also attenuated by ANF infusions in patients as well as in healthy volunteers, indicating a role for ANF in anxiety.
The central corticotropin-releasing factor (CRF)-ergic system is known to play a critical role in anxiety and other behavioral stress responses. It has been shown that ANF, but also BNP and CNP, exert anxiolytic-like effects in behavioral studies.
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