Hypertension due to blockade of NF-kappaB during nephrogenesis: effect of a high-salt diet

• Grant number: 11/17773-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2011
• End date: June 30, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Clarice Kazue Fujihara
• Grantee: Victor Ferreira de Ávila
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Angiotensin II (Ang II) participates in the progression of chronic kidney disease through the activation of several signaling pathways, such as calcium mobilization and activation of protein kinases, activator protein-1 (AP-1) and nuclear factor kB (NF-kB). Once activated, NF-kB controls the gene expression of several pro-inflammatory agents, increasing the expression of monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2), cytokines, adhesion molecules, iNOS and endothelin.Administration Losartan during murine lactation causes progressive renal injury, indicating a physiologic action of angiotensin II on nephrogenesis. Recently we developed a study in which the NF-ºB system was blocked by administration of pyrrolidinedithiocarbamate (PDTC) during the final phase of nephrogenesis. Immediately after birth, the animals received PDTC for 20 days and were followed until 10 months of age. Animals treated with PDTC during lactation developed hypertension in adulthood without developing progressive nephropathy as observed in animals that received Losartan instead. One possible reason for the development of hypertension in these animals is the presence of tubulointerstitial changes, wich may have changed the renal excretion of sodium. These results indicate that the NF-ºB system also participates in organogenesis, but in a more subtle way than Ang II and that its absence during nephrogenesis promotes hypertension and cardiac fibrosis without causing severe renal impairment.The aim of this study is to verify whether that a second insult, such as saline overload, will cause more severe hypertension, cardiac and renal lesion in animals with blockade of the NF-ºB during lactation.