Differential regulation of angiotensinogen and natriuretic peptide mRNAs in rat brain by osmotic stimulation: focus on anterior hypothalamus and supraoptic nucleus.

Abstract

Central angiotensin II and natriuretic peptide systems have been shown to be involved in the central regulation of blood fluid homeostasis with alterations in central peptide and/or receptor levels observed following changes in osmotic status. The present study investigated the effects of sodium loading on mRNA encoding the angiotensin II precursor, angiotensinogen (AOGEN), and the natriuretic peptides, atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) in rat brain using quantitative in situ hybridization histochemistry of [35S]- and [33P]-labeled oligonucleotide probes. Following 7 and 14 days of 2% sodium chloride in drinking water a significant increase was detected in preproAOGEN (ppAOGEN) mRNA in presumed astrocytes in regions of the anterior hypothalamus, including the periventricular nucleus, the medial preoptic area and medial preoptic nucleus, while a decrease was observed in astrocytes in the supraoptic nucleus. Other forebrain regions examined including the subfornical organ, bed nucleus of the stria terminalis and the arcuate nucleus showed no significant alteration in the level of ppAOGEN mRNA. Sodium loading did not appreciably alter ppANP or ppCNP mRNA levels in neurons of the anteromedial preoptic or arcuate nuclei or hippocampus at the times studied. PpANP mRNA levels were also unaltered in Barrington's nucleus following sodium loading, while preprocorticotropin-releasing hormone mRNA was significantly decreased. These results indicate that AOGEN mRNA transcription/stability in vivo is modulated by alterations in osmotic balance, consistent with previous reports of a central role for AII in cardiovascular and body fluid homeostasis. In contrast, despite reports of modulation of hypothalamic ANP-immunoreactivity following changes in osmotic status, it would appear that osmotic stimulation over periods of 7-14 days does not markedly alter the transcription or stability of hypothalamic natriuretic peptide mRNAs in vivo.