Natriuretic peptide receptor A mediates renal sodium excretory responses to blood volume expansion.
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
Shang-Jin
SJ
Department of Physiology, Tulane University Health Sciences Center School of Medicine, New Orleans, LA 70112, USA.
Vellaichamy
Elangovan
E
Chin
So Yeon
SY
Smithies
Oliver
O
Navar
L Gabriel
LG
Pandey
Kailash N
KN
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D001798:Blood Proteins / Q000032:analysis; D001810:Blood Volume / Q000502:physiology*; D006152:Cyclic GMP / Q000652:urine; D004231:Diuresis / Q000502:physiology; D018628:Gene Dosage; D020440:Gene Duplication; D005919:Glomerular Filtration Rate / Q000502:physiology; D006162:Guanylate Cyclase / Q000235:genetics / Q000502:physiology*; D006400:Hematocrit; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009318:Natriuresis / Q000502:physiology*; D009994:Osmolar Concentration; D011188:Potassium / Q000652:urine; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology
D001798:Blood Proteins; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D006152:Cyclic GMP; D011188:Potassium