Local modulation of the natriuretic peptide system in the rat remnant kidney

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Carla Santos Araújo (Author) FMUP; Roberto Roncon Albuquerque Jr (Author) FEUP; Mónica Moreira Rodrigues (Author) ICBAS; Tiago Henriques Coelho (Author) Other; Janete Quelhas Santos (Author) FMUP; Bernardo Faria (Author) Other; Benedita Sampaio Maia (Author) FMDUP; Adelino F. Leite Moreira (Author) FMUP; Manuel Pestana (Author) FMUP

Journal

Title: Nephrology Dialysis Transplantation

Vol. 24 No. 6

Pages: 1774-1782

ISSN: 0931-0509

Publisher: Oxford University Press

Indexing

ISI Web of Knowledge - 9 Citations

ISI Web of Science

Scopus - 10 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences

Other information

Authenticus ID: P-003-JVP

DOI: 10.1093/ndt/gfn719

Abstract (EN): 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 (3/4nx) rats, up to 26 weeks after surgery. Methods. Male Wistar-Han rats (190-220 g; n = 49) were randomly assigned to 3/4nx 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 3/4nx 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 3/4nx 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 3/4nx 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 3/4nx rats. Conclusions. BP elevation and compromised natriuretic response to VE in 3/4nx rats is associated with increased circulating BNP levels in the absence of cardiac dysfunction. This is accompanied in 3/4nx 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9