| First Author | Shi SJ | Year | 2001 |
| Journal | Am J Physiol Renal Physiol | Volume | 281 |
| Issue | 4 | Pages | F665-73 |
| PubMed ID | 11553513 | Mgi Jnum | J:114413 |
| Mgi Id | MGI:3688970 | Doi | 10.1152/ajprenal.2001.281.4.F665 |
| Citation | Shi SJ, et al. (2001) Genetic disruption of atrial natriuretic peptide receptor-A alters renin and angiotensin II levels. Am J Physiol Renal Physiol 281(4):F665-73 |
| abstractText | We have studied cardiovascular and renal phenotypes in Npr1 (genetic determinant of natriuretic peptide receptor-A; NPRA) gene-disrupted mutant mouse model. The baseline systolic arterial pressure (SAP) 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-copy, 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 microg 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 renin concentrations (PRCs) and in expression of renal renin message compared with 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 RAAS is a compensatory response that prevents greater increases in elevated arterial pressures in adult NPRA null mutant mice. However, the greater renin 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. |
