B and C types natriuretic peptides modulate norepinephrine uptake and release in the rat hypothalamus

We previously reported that atrial natriuretic factor (ANF) regulates catecholamine metabolism in the central nervous system. ANF, B and C types natriuretic peptides (BNP and CNP) also play a regulatory role in body fluid homeostasis, cardiovascular activity and hormonal and neuro-hormonal secretions. The aim of the present work was to investigate BNP and CNP effects on the uptake and release of norepinephrine (NE) in rat hypothalamic slices incubated in vitro. Results showed that BNP (100 nM) and CNP (1, 10 and 100 nM) enhanced total and neuronal [3H]NE uptake but did not modify non-neuronal uptake. BNP (100 nM) and CNP (1 nM) caused a rapid increase in NE uptake (1 min), which was sustained for 60 min. BNP (100 nM) did not modify the intracellular distribution of NE; however, 1 nM CNP increased the granular store and decreased the cytosolic pool of NE. BNP (100 nM) and CNP (1, 10 and 100 nM), diminished spontaneous NE release. In addition, BNP (1, 10, 100 nM) and CNP (1, 10 and 100 pM, as well as 1, 10 and 100 nM) reduced NE output induced by 25 mM KCl. These results suggest that BNP and CNP may be involved in the regulation of several central as well as peripheral physiological functions through the modulation of noradrenergic neurotransmission at the presynaptic neuronal level. Present results provide evidence to consider CNP as the brain natriuretic peptide since physiological concentrations of this peptide (pM) diminished NE evoked release.