Neuron- or glial-specific ablation of secreted renin does not affect renal renin, baseline arterial pressure, or metabolism.

Abstract:

:The renin-angiotensin system (RAS), known for its roles in cardiovascular, metabolic, and developmental regulation, is present in both the circulation and in many individual tissues throughout the body. Substantial evidence supports the existence of a brain RAS, though quantification and localization of brain renin have been hampered by its low expression levels. We and others have previously determined that there are two isoforms of renin expressed in the brain. The classical isoform encoding secreted renin (sREN) and a novel isoform encoding intracellular renin (icREN), the product of an alternative promoter and first exon (exon 1b). The differential role that these two isoforms play in cardiovascular and metabolic regulation remains unclear. Here we examined the physiological consequences of neuron- and glia-specific knockouts of sREN by crossing mice in which the sREN promoter and isoform-specific first exon (exon-1a) is flanked by LoxP sequences (sREN(flox) mice) with mice expressing Cre-recombinase controlled by either the neuron-specific Nestin promoter or the glia-specific GFAP promoter. Resulting offspring exhibited selective knockout of sREN in either neurons or glia, while preserving expression of icREN. Consistent with a hypothesized role of icREN in the brain RAS, neuron- and glia-specific knockout of sREN had no effect on blood pressure or heart rate; food, water, or sodium intake; renal function; or metabolic rate. These data demonstrate that sREN is dispensable within the brain for normal physiological regulation of cardiovascular, hydromineral, and metabolic regulation, and thereby indirectly support the importance of icREN in brain RAS function.

journal_name

Physiol Genomics

journal_title

Physiological genomics

authors

Xu D,Borges GR,Davis DR,Agassandian K,Sequeira Lopez ML,Gomez RA,Cassell MD,Grobe JL,Sigmund CD

doi

10.1152/physiolgenomics.00208.2010

subject

Has Abstract

pub_date

2011-03-29 00:00:00

pages

286-94

issue

6

eissn

1094-8341

issn

1531-2267

pii

physiolgenomics.00208.2010

journal_volume

43

pub_type

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