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Int J Physiol Pathophysiol Pharmacol 2012;4(3):128-139

Original Article
Disruption of Npr1 gene differentially regulates the juxtaglomerular and distal
tubular renin levels in null mutant mice

Minolfa C Prieto, Subhankar Das, Naveen K Somanna, Lisa M Harrison-Bernard, L Gabriel Navar, Kailash N Pandey

Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA 70112; Department of Physiology, LSU Health
Sciences Center, New Orleans, LA 70112, USA.

Received August 12, 2012; accepted September 7, 2012; Epub September 20, 2012; Published September 30, 2012

Abstract: 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.

Keywords: Distal tubular and juxtaglomerular renin, immunohistochemistry, atrial natriuretic peptide receptor-A, gene-disrupted mice,

Address all correspondence to:
Dr. Kailash N Pandey
Department of Physiology SL39
Tulane University Health Science Center
New Orleans, LA 70112, USA.
Tel: (504) 584-1628; Fax: (504) 584-2675
E-mail: kpandey@tulane.edu