Details

Autor(en) / Beteiligte

• Imai, Hiroe

Titel

Mechanism of Progression of Renal Insuffi ciency in Rat with Glomerulosclerosis

Ist Teil von

• Journal of Saitama Medical University, 2002, Vol.29(1), pp.35-50

Ort / Verlag

The Medical Society of Saitama Medical University

Erscheinungsjahr

2002

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Objective: To investigate the role of the renin-angiotensin system and sodium in the pathogenesis of glomerulosclerosis, I examined the effect of angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) on blood pressure and renal function in rat with glomerulosclerosis, Milan normotensive rats (MNS). Method: Experiment 1: Twenty-four 8-week old MNS were divided into three groups as follows (1) Normal-salt diet group (0.5％NaCl), (2) Low-salt diet group (0.1％NaCl), and (3) High-salt diet group (6.0％NaCl). Each diet was given for 32 weeks. Experiment 2: Twenty-four 8-week old MNS were divided into three groups as follows (1) ACEI treated group (Delapril 10mg/kg/day), (2) ARB treated group (CV-116 3mg/kg/day), and (3) placebo treated group (control). Each of these antihypertensive drug was administrated per os for 32 weeks. In both studies, during the experiment, body weight, blood pressure and urinary excretion of protein were measured every four weeks. At the end of study, after measurement of plasma angiotensin I, angiotensin II, aldosterone and renin activity, renal tissues were obtained for light microscopic examination and for measurements of AT1a receptor, AT2 receptor, ecNOS and HO-1 mRNA by using RT-PCR. Results: Experiment 1: During the experiment, renin-angiotensin system was high level in normal salt-diet group and it was more activated in low salt-diet. There were no significant differences in blood pressure in three groups. Marked glomerulosclerosis and interstitial cell infiltration, which were found in MNS were significantly aggravated by low-salt diet. On the contrary, glomerular changes were significantly ameliorated by high-salt diet. Experiment 2: Systolic blood pressure and urinary excretion of protein in MNS was significantly reduced by administration of ACEI. ACEI treatment induced significant elevation of the expression of AT2 receptor, ecNOS and HO-1 mRNA in the kidney. ARB treatment induced significant reduction of the expression of ecNOS and HO-1 mRNA in the kidney. Marked glomerulosclerosis and interstitial cell infiltration, which were found in the control group were significantly ameliorated by treatment of ACEI. On the contrary, there was no significant improvement in ARB treated group. Conclusion: From these data, I concluded that histopathological change in the kidney in MNS was determined by the activation of renin-angiotensin system. On the contrary, nitric oxide and heme-oxygenase plays as the protective role in the renal insufficiency. Furthermore, ACEI and ARB were different from renalprotective effect in rat with glomerulosclerosis.