Natriuretic peptide receptor A mediates renal sodium excretory responses to blood volume expansion

• Published in: American journal of physiology. Renal physiology Vol. 54; no. 4; pp. F694 - F702
• Main Authors: SHI, Shang-Jin, VELLAICHAMY, Elangovan, SO YEON CHIN, SMITHIES, Oliver, NAVAR, L. Gabriel, PANDEY, Kailash N
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.10.2003
• Subjects: Biological and medical sciences; Blood; Fundamental and applied biological sciences. Psychology; Kidneys; Neurotransmitters; Peptides; Vertebrates: urinary system; Urine; Excretion; gene disruption; Rodentia; 3',5'-GMP; cGMP; Volume expansion; Atrial natriuretic peptide; Kidney; Vertebrata; Natriuretic hormone; Mammalia; Urinary system; Mouse; Blood volume; Animal; gene duplication; Sodium ion; Peptidergic receptor; Hemodynamics; sodium excretion
• ISSN: 1931-857X; 1522-1466

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 (µl min-1 g kidney wt-1) increased from 4.9 ± 1.0 to 14.4 ± 1.8 and sodium excretion (µeq min-1 g kidney wt-1) from 1.15 ± 0.22 to 3.11 ± 0.60, associated with a rise in glomerular filtration rate (GFR; ml min-1 g kidney wt-1) from 0.63 ± 0.03 to 0.82 ± 0.09 and renal plasma flow (RPF; ml 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.