ANP-mediated inhibition of distal nephron fractional sodium reabsorption in wild-type and mice overexpressing natriuretic peptide receptor.
Atrial natriuretic peptide (ANP) elicits natriuresis; however, the relative contributions of proximal and distal nephron segments to the overall ANP-induced natriuresis have remained uncertain. This study was performed to characterize the effects of ANP on distal nephron sodium reabsorption determined after blockade of the two major distal nephron sodium transporters with amiloride (5 microg/g body wt) plus bendroflumethiazide (12 microg/g body wt) in male anesthetized C57/BL6 and natriuretic peptide receptor-A gene (Npr1) targeted four-copy mice. The lower dose of ANP (0.1 ng x g body wt(-1) x min(-1), n = 6) increased distal sodium delivery (DSD, 2.4 +/- 0.4 vs. 1.6 +/- 0.2 mueq/min, P < 0.05) but did not change fractional reabsorption of DSD compared with control (86.3 +/- 2.0 vs. 83.9 +/- 3.6%, P > 0.05), thus limiting the magnitude of the natriuresis. In contrast, the higher dose (0.2 ng x g body wt(-1) x min(-1), n = 6) increased DSD (2.8 +/- 0.3 mueq/min, P < 0.01) and also decreased fractional reabsorption of DSD (67.4 +/- 4.5%, P < 0.01), which markedly augmented the natriuresis. In Npr1 gene-duplicated four-copy mice (n = 6), the lower dose of ANP increased urinary sodium excretion (0.6 +/- 0.1 vs. 0.3 +/- 0.1 mueq/min, P < 0.05) and decreased fractional reabsorption of DSD compared with control (72.2 +/- 3.4%, P < 0.05) at similar mean arterial pressures (91 +/- 6 vs. 92 +/- 3 mmHg, P > 0.05). These results provide in vivo evidence that ANP-mediated increases in DSD alone exert modest effects on sodium excretion and that inhibition of fractional reabsorption of distal sodium delivery is requisite for the augmented natriuresis in response to the higher dose of ANP or in Npr1 gene-duplicated mice.
Zhao
Di
D
Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center School of Medicine, New Orleans, Louisiana 70112, USA. dzhao@tulane.edu
Pandey
Kailash N
KN
Navar
L Gabriel
LG
D000042:Absorption; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D001539:Bendroflumethiazide / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*
D004232:Diuretics; D001539:Bendroflumethiazide; D000584:Amiloride; D009320:Atrial Natriuretic Factor; D012964:Sodium; D017461:Receptors, Atrial Natriuretic Factor