Atrial natriuretic factor inhibits norepinephrine biosynthesis and turnover in the rat hypothalamus

We have previously reported that atrial natriuretic factor (ANF) increased neuronal norepinephrine (NE) uptake and reduced basal and evoked neuronal N E release. Changes in NE uptake and release are generally associated to mod ifications in the synthesis and/or turnover of the amine. On this basis, th e aim of the present work was to study ANF effects in the rat hypothalamus on the following processes: endogenous content, utilization and turn-over o f NE; tyrosine hydroxylase (TH) activity; cAMP and cGMP accumulation and ph osphatidylinositol hydrolysis. Results showed that centrally applied ANF (1 00 ng/mu 1/min) increased the endogenous content of NE (45%) and diminished NE utilization. Ten nM ANF reduced the turnover of NE (53%). In addition, ANF (10 nM) inhibited basal and evoked (with 25 mM KCl) TH activity (30 and 64%, respectively). Cyclic GMP levels were increased by 10 nM ANF (100%). However, neither cAMP accumulation nor phosphatidylinositol breakdown were affected in the presence of 10 nM ANF. The results further support the role of ANF in the regulation of NE metabolism in the rat hypothalamus. ANF is likely to act as a negative putative neuromodulator inhibiting noradrenergi c neurotransmission by signaling through the activation of guanylate cyclas e. Thus, ANF may be involved in the regulation of several central as well a s peripheral physiological processes such as cardiovascular function, elect rolyte and fluid homeostasis, endocrine and neuroendocrine synthesis and se cretion, behavior, thirst, appetite and anxiety that are mediated by centra l noradrenergic activity. (C) 1999 Elsevier Science B.V. All rights reserve d.