In mice, NPRA activation via Npr1 gene copy number predominantly mediates the natriuretic, diuretic, and renal hemodynamic responses to acute blood volume expansion.
NPRA activation is the predominant mechanism mediating natriuretic, diuretic, and renal hemodynamic responses to acute blood volume expansion in mice.
valor p: p=<0.001
The deficiency of Npr1 genetic determinant of natriuretic peptide receptor A (NPRA) increases arterial pressures and causes hypertensive heart disease in mice similar to those seen in untreated human hypertensive patients. However, the quantitative role of NPRA in mediating the renal responses to blood volume expansion remains uncertain. To determine the specific contribution of NPRA in mediating the signaling mechanisms responsible for natriuretic and diuretic responses to nondilutional intravascular expansion, we administered whole blood to anesthetized Npr1 homozygous null mutant (0-copy), wild-type (2-copy), and gene-duplicated (4-copy) mice. In wild-type (2-copy) animals, urinary flow (microl x min-1 x g kidney wt-1) increased from 4.9 +/- 1.0 to 14.4 +/- 1.8 and sodium excretion (microeq x min-1 x g kidney wt-1) from 1.15 +/- 0.22 to 3.11 +/- 0.60, associated with a rise in glomerular filtration rate (GFR; ml x min-1 x g kidney wt-1) from 0.63 +/- 0.03 to 0.82 +/- 0.09 and renal plasma flow (RPF; ml x min-1. g kidney wt-1) from 2.96 +/- 0.17 to 4.36 +/- 0.41, whereas arterial pressure did not significantly increase. After volume expansion, 0-copy mice showed significantly lesser increases in urinary flow (P < 0.001) and sodium excretory (P < 0.001) responses even though the increases in arterial pressures were greater (P < 0.001) compared with 2-copy mice. The 4-copy mice showed augmented responses in urinary flow (P < 0.01) and sodium excretion (P < 0.001) along with rises in both GFR (P < 0.01) and RPF (P < 0.01) compared with 2-copy wild-type mice. These results establish that NPRA activation is the predominant mechanism mediating the natriuretic, diuretic, and renal hemodynamic responses to acute blood volume expansion.
Shi et al. (Wed,) reported a other. Whole blood administration (blood volume expansion) vs. Wild-type (2-copy) mice was evaluated on Urinary flow and sodium excretion (p=<0.001). In mice, NPRA activation via Npr1 gene copy number predominantly mediates the natriuretic, diuretic, and renal hemodynamic responses to acute blood volume expansion.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: