Sj. Shi et al., Genetic disruption of atrial natriuretic peptide receptor-A alters renin and angiotensin II levels, AM J P-REN, 281(4), 2001, pp. F665-F673
We have studied cardiovascular and renal phenotypes in Npr1 (genetic determ
inant of natriuretic peptide receptor-A; NPRA) gene-disrupted mutant mouse
model. The baseline systolic arterial pressure (SA-P) in 0-copy mutant (-/-
) mice (143 +/- 2 mmHg) was significantly higher than in 2-copy wild-type (
+/+) animals (104 +/- 2 mmHg); however, the SAP in 1-copy heterozygotes (+/
-) was at an intermediate value (120 +/- 4 mmHg). To determine whether Npr1
gene function affects the renin-angiotensin-aldosterone system (RAAS), we
measured the components of RAAS in plasma, kidney, and adrenal gland of 0-c
opy, 1-copy, and 2-copy male mice. Newborn (2 days after the birth) 0-copy
pups showed 2.5-fold higher intrarenal renin contents compared with 2-copy
wild-type counterparts (0-copy 72 +/- 12 vs. 2-copy 30 +/- 7 mug ANG I . mg
protein(-1). -h(-1), respectively). The intrarenal ANG II level in 0-copy
pups was also higher than in 2-copy controls (0-copy 33 +/- 5 vs. 2-copy 20
+/- 2 pg/mg protein, respectively). However, both young (3 wk) and adult (
16 wk) 0-copy mutant mice showed a dramatic 50-80% reduction in plasma reni
n concentrations (PRCs) and in expression of renal renin message compared w
ith 2-copy control animals. In contrast, the adrenal renin content and mRNA
expression levels were 1.5- to 2-fold higher in 0-copy adult mice than in
2-copy animals. The results suggest that inhibition of renal and systemic R
AAS is a compensatory response that prevents greater increases in elevated
arterial pressures in adult NPRA null mutant mice. However, the greater ren
in and ANG II levels seen in 0-copy newborn pups provide evidence that the
direct effect of NPRA activation on renin is an inhibitory response.