Cardiac cachexia and altered left ventricular hemodynamic and molecular parameters in puromycin aminonucleoside (PAN)-induced nephrotic syndrome.

• Type: Summary of Presentation in an International Conference
• Date: 2005

Authors

Moreira-Rodrigues M (Author) Other; Roncon-Albuquerque R Jr (Author) FMUP; Henriques-Coelho T (Author) FMUP; Sampaio-Maia B (Author) Other; Leite-Moreira AF (Author) FMUP

Conference proceedings International

Title: Nephrology Dialysis Transplantation

Initial page: V42

42nd Annual Meeting of the European-Renal-Association/European-Dialysis-and-Transplant-Association (ERA-EDTA)

Istanbul, TURKEY, 04 a 07 Junho de 2005

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Resumo (PT): Enhanced sodium retention in the nephrotic syndrome was attributed to blunted renal response to natriuretic peptides produced in the heart. Also, the nephrotic state was associated with increased plasma levels of TNF-a, a cytokine involved in muscular cachexia, myocardial structural remodeling and left ventricular (LV) dysfunction. However, the cardiac repercussions of these findings were not examined. The aim of the present study was to evaluate LV hemodynamics, myocardial molecular remodeling and cachexia parameters in PAN-induced nephrosis. Sprague-Dawley rats (150±10g) were injected with PAN (150 mg/kg bw, ip; n=7) or with vehicle (0,9% NaCl; n=7) on day 0. The two groups of animals were placed in metabolic cages, were given the same quantity of food and the time courses of the urinary excretion of sodium and proteins were examined. On days 7 and 14 the PAN-treated and control rats were anesthesiated and LV pressures were evaluated using a tip micromanometer. Afterload elevations were performed by aortic occlusions to obtain isovolumetric (iso) cycles. The tibial length was measured and the heart, gastrocnemius muscle and ascites volume were weighted. Thereafter, LV samples were collected formRNA quantification (RT-PCR), using GAPDH as the housekeeping gene. The PAN-treated rats developed severe proteinuria on day 4, reaching a plateau on day 8. The greatest sodium retention and ascites accumulation in PAN-treated rats was observed on day 7. The PAN-treated rats presented an increase in BNPmRNAlevels only on day 7 (264±54%) whereas cachexia parameters were observed in PAN-treated rats only on day 14 (∼46% decrease in gastrocnemius muscle weight/tibial length; ∼15% decrease in heart weight/tibial length).An upregulation in TNF-amRNA levels was observed in the LV from PAN-treated rats on both days 7 (193±61%) and 14 (275±66%). By contrast, no significant differences were observed in IGF- 1 mRNA levels in LV between PAN-treated and control rats either on day 7 or 14. On day 7, a diastolic intolerance to afterload was observed in PANtreated rats (ISOEDP in mmHg: 5.3±0.7 vs. 2.4±0.5) without changes in relaxation or contractility. On day 14, the PAN-treated rats presented systolic dysfunction (ISOPmax in mmHg: 164.8±14.2 vs. 205±5.5; ISOdP/dtmax in mmHg/s: 4011.5±398.5 vs. 5784.4±532.8), slower relaxation rate (ISOTau in ms: 33.7±3.2 vs. 20.4±1.2; PANiso) and diastolic dysfunction (ISOEDP in mmHg: 5.9±0.8 vs. 2.1±0.5). It is concluded that PAN nephrosis is accompanied with progressive muscular and cardiac cachexia going along with both systolic and diastolic dysfunction. This might be related with upregulation of TNF-a mRNA levels in the LV, in a state of proteinuria. Supported by POCTI/FCB/45660/2002 FCT

Language: Portuguese

Type (Professor's evaluation): Scientific

Notes: XLII Congress of the ERA-EDTA 42nd Annual Meeting of the European-Renal-Association/European-Dialysis-and-Transplant-Association (ERA-EDTA), published in journal, Nephrology Dialysis Transplantation 2005; Vol.20(Suppl.5):V42.