Local modulation of the natriuretic peptide system in the rat remnant kidney.
BACKGROUND
The natriuretic peptide (NP) system plays a central role in the renal adaptations to acute volume expansion. However, the modulation of the NP system in chronic renal insufficiency (CRI) remains to be elucidated. In the present study, we evaluated cardiac haemodynamics, plasma type-B natriuretic peptide (BNP) levels and the expression of natriuretic peptide receptor A (NPR-A) and NPR-C in the renal cortex (RC) and medulla (RM) of Sham and (3/4) nephrectomized ((3/4)nx) rats, up to 26 weeks after surgery.


METHODS
Male Wistar-Han rats (190-220 g; n = 49) were randomly assigned to (3/4)nx or Sham surgery. Two, 10 and 26 weeks after surgery, non-invasive blood pressure (BP) and left ventricular (LV) haemodynamics were performed, and urine and blood were collected for metabolic studies and plasma BNP determination. In addition, tissue samples from RC and RM were obtained for NPR-A and NPR-C quantification (RT-PCR and western blotting) as well as NPR-A immunodetection.


RESULTS
In (3/4)nx rats, the progressive interstitial fibrosis and tubular atrophy were accompanied by a time-dependent increase of BP and impaired natriuretic response to volume expansion (VE). This was accompanied in (3/4)nx rats by an early and time-dependent elevation of BNP circulating levels that was not associated with cardiac dysfunction or increased myocardial BNP gene expression. In (3/4)nx rats, NPR-A expression in the remnant RM was consistently reduced at 2, 10 and 26 weeks, and this was accompanied by an increase in NPR-C expression in the remnant RC from (3/4)nx rats.


CONCLUSIONS
BP elevation and compromised natriuretic response to VE in (3/4)nx rats is associated with increased circulating BNP levels in the absence of cardiac dysfunction. This is accompanied in (3/4)nx rats by both impaired NPR-A expression in the RM and upregulation of NPR-C in the RC suggesting a novel mechanism for NP resistance in CRI.
Santos-Araújo
Carla
C
Unit of Research and Development of Nephrology, Department of Physiology, Faculty of Medicine, Porto, Portugal.
Roncon-Albuquerque
Roberto
R
Moreira-Rodrigues
Mónica
M
Henriques-Coelho
Tiago
T
Quelhas-Santos
Janete
J
Faria
Bernardo
B
Sampaio-Maia
Benedita
B
Leite-Moreira
Adelino F
AF
Pestana
Manuel
M
D000818:Animals; D001483:Base Sequence; D001810:Blood Volume / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D006439:Hemodynamics / Q000502:physiology; D007672:Kidney Cortex / Q000503:physiopathology; D007679:Kidney Medulla / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000502:physiology; D045265:Natriuretic Peptides / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics / Q000502:physiology; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
D017931:DNA Primers; D045265:Natriuretic Peptides; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C