Role of Renin-Angiotensin System on Liver Regeneration after Massive Hepatectomy

• Grant number: 08/08724-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2009
• End date: December 31, 2009
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Fernando Silva Ramalho
• Grantee: Nayara Tognon
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The hepatic regenerative phenomenon is recognized as a singular example of ordered and organized tissue growth. In experimental animals, the liver regeneration has been extensively studied after 70% partial hepatectomy (PH), which consists in the resection of the left lateral and medium lobes. The cell proliferation following 70% PH begins 24 hours after surgery, and the peak of proliferative response occurs 34 hours after 70% PH in rats. Eighty five percent of the hepatocytes synthesize DNA during the first three days after surgery, and liver regeneration is usually completed in 7 to 10 days. Recent studies demonstrated that 90% PH is the limit for successful rat hepatectomy, whereas 95% of the liver resection resulted in 100% mortality within 96 hours after surgery. Thus, 95% PH (massive hepatectomy) seems to be a good surgical experimental model of acute and fatal liver failure. The Renin-Angiotensin System (RAS) is widely known by its central role on regulation of blood pressure and renal sodium and water absorption. More recently, however, it has been demonstrated the primary expression of the RAS components in several individual tissues, which supports an important function of the local or paracrine RAS on physiology of different organs. Actual studies evidenced that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor type 1 (ART1) antagonists may stimulate liver regeneration after 70% PH in rats. Angiotensin II exhibits a potent inhibitory effect on hepatocellular proliferation, and the use of the ART1 blockers increases hepatic proliferative activity. The purpose of the present study is evaluate gene expression of the RAS components on livers subjected to 95% and 70% PH, as well as verifies the effects of the ACE inhibitors and ART1 antagonists on liver regeneration after massive hepatectomy in rats.