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Publication : Disruption of Npr1 gene differentially regulates the juxtaglomerular and distal tubular renin levels in null mutant mice.

First Author  Prieto MC Year  2012
Journal  Int J Physiol Pathophysiol Pharmacol Volume  4
Issue  3 Pages  128-39
PubMed ID  23071870 Mgi Jnum  J:197580
Mgi Id  MGI:5493391 Citation  Prieto MC, et al. (2012) Disruption of Npr1 gene differentially regulates the juxtaglomerular and distal tubular renin levels in null mutant mice. Int J Physiol Pathophysiol Pharmacol 4(3):128-39
abstractText  Atrial natriuretic peptide (ANP) exerts an inhibitory effect on juxtaglomerular (JG) renin synthesis and release by activating guanylyl cyclase/ natriuretic peptide receptor-A (GC-A/NPRA). Renin has also been localized in connecting tubule cells; however, the effect of ANP/NPRA signaling on tubular renin has not been determined. In the present study, we determined the role of NPRA in regulating both JG and tubular renin using Npr1 (coding for NPRA) gene-disrupted mice, which exhibit a hypertensive phenotype. Renin-positive immunoreactivity in Npr1(-/-) homozygous null mutant mice was significantly reduced compared with Npr1(+/+) wild-type mice (23% vs 69% renin-positive glomeruli). However, after chronic diuretic treatment, Npr1(-/-) mice showed an increment of JG renin immunoreactivity compared with Npr1(+/+) mice (70% vs 81% renin-positive glomeruli). There were no significant differences in the distal tubule renin between Npr1(+/+) and Npr1(-/-) mice. However, after diuretic treatment, Npr1(-/-) mice showed a significant decrease in renin immunoreactivity in principal cells of cortical collecting ducts (p<0.05). The increased JG renin immunoreactivity after reduction in blood pressure in diuretic-treated Npr1(-/-) mice, demonstrates an inhibitory action of ANP/NPRA system on JG renin; however, a decreased expression of distal tubular renin suggests a differential effect of ANP/NPRA signaling on JG and distal tubular renin.
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