RESUMEN
Objective To observe the effects of angiotensin Ⅱ( Ang Ⅱ) blockade on renal function, renal blood flow and renal oxygen consumption in chronic renal failure ( CRF) rats induced by 5/6th kidney ablation /infarction (5/6A/I).Methods Sprague-Dawley rats were randomly divided into 3 groups:the normal group (group A, n =14), mod-el group (group B, n=14) and angiotensin II blockade (Cozaar with Monopril) treatment group (group C, n =14).The chronic renal failure ( CRF) rat models were induced by 5/6th kidney ablation/infarction.The tail artery systolic pressure (SBP), diastolic blood pressure (DBP) and tail vein serum creatinine (Scr), blood urea nitrogen (BUN), hemoglobin ( Hb) and creatinine clearance rate ( Ccr) were assessed before and after intervention.The course of treatment was sixty days.The renal blood flow ( RBF) , blood gas analysis of abdominal aortic and renal vein, left renal vein pressure ( RV-pO2 ) were detected and remnant renal oxygen consumption ( QO2/TNa ) was calculated, and the pathological changes of remnant kidney were observed after the 60 d intervention.Results (1) Compared with the group A, the levels of Scr, BUN and tail artery SBP, DBP were significantly increased ( P<0.01 for all) , and the levels of Ccr and Hb were signifi-cantly decreased ( P<0.01) in the groups B and C, demonstrating the successful modeling.(2) Compared with the group B, the levels of Scr, tail artery SBP, DBP and QO2/TNa were significantly decreased (P<0.01 for all), the levels of BUN were decreased (P<0.05), the levels of Hb, Ccr and RVpO2 were significantly increased (P<0.01 for all), the level of RBF was increased ( P<0.05) in the group C after intervention.(3) The histopathological examination of the remnant re-nal tissue showed that the pathological changes in the group C were apparently reduced, better than those of the Group B. Conclusions Angiotensin II blockade can increase RBF, reduce renal oxygen consumption, improve renal function, and reduce the renal pathological changes in CRF rats.The mechanism of renal protection may be related to the regulation of cellular energy metabolism and improvement of renal oxygen consumption.
RESUMEN
BACKGROUND: Long-term treatment of immunosuppresant CsA causes interstitial inflammation and fibrosis in the kidney. Renin-angiotensin system (RAS) plays the most important role in the pathogenesis CsA-induced renal injury. Accordingly we evaluated the anti-inflammatory effect of angiotensin II blockades using losartan (LSRT) in a rat model of chronic CsA nephropathy. METHODS: Male Sprague-Dawley rats, initially weighing 225 to 250 g, were used. After 1 week of a low-salt diet (0.05% sodium), the rats were randomized into four groups and treated for 4 weeks. The Vehicle (VH) group was treated with olive oil. The VH+LSRT group was treated with olive oil and LSRT. The CsA group received CsA. The CsA+LSRT group was simultaneously treated with CsA and LSRT. The anti-inflammatory effect of LSRT was evaluated with C-reactive protein (CRP) expression, osteopontin (OPN) mRNA and protein expression, and ED-1 infiltration RESULTS: The CsA treatment caused an increase in serum creatinine and a decrease in creatinine clearance compared with that of the VH group. Intrarenal CRP positive cells were significantly decreased in the CsA+LSRT group compared with the CsA group (38.0 +/- 2.1 vs. 65.0 +/- 5.1, p<0.01). In the CsA group, the degree of OPN mRNA expression was increased compared with that of the VH group. But, OPN mRNA expression was decreased in the CsA+LSRT group (387.5 +/- 56.6% vs. 719.8 +/- 58.5%, p<0.05). In the degree of ED-1 infiltration, we had a similar results such as CRP and OPN mRNA expression (CsA group 30.5 +/- 8.0 vs. CsA+LSRT 86.0 +/- 11.0, p<0.01). CONCLUSION: We concluded that the anti-inflammatory effects of angiotensin II blockade has a potential protective effect against CsA-induced renal injury.