Persistent hypertension and progressive renal injury induced by salt overload after short term nitric oxide inhibition

被引:12
作者
Mattar, Ana Lucia [1 ]
Machado, Flavia Gomes [1 ]
Fujihara, Clarice Kazue [1 ]
Malbeiros, Denise Maria Avancini Costa [1 ]
Zatz, Roberto [1 ]
机构
[1] Univ Sao Paulo, Fac Med, Dept Clin Med, Div Renal, Sao Paulo, Brazil
关键词
chronic kidney disease; mycophenolate mofetil; angiotensin II; AT-1 receptor blocker; salt overload;
D O I
10.1590/S1807-59322007000600015
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
INTRODUCTION: Administration of the NO inhibitor N-w delta-nitro-L-arginine methyl ester (NAME) and a high-salt diet (HS) promotes severe albuminuria and renal injury, which regresses upon discontinuation of treatments. OBJECTIVE: We investigated whether these changes reappear after reinstitution of HS, and whether they are prevented by treatment with the antilymphocyte agent mycophenolate mofetil (MMF) or the AT-1 receptor blocker losartan (L). Adult male Munich-Wistar rats received NAME and HS. A control Group (C) received only HS. After 20 days, rats receiving HS and NAME exhibited severe hypertension and albuminuria. After a 30-day recovery period, hypertension was attenuated and albuminuria had virtually disappeared. MATERIAL AND METHODS: Rats were then distributed among the following groups: HS, receiving HS; NS, receiving a normal salt (NS) diet; HS-MMF, receiving HS and MMF; HS-LOS, receiving HS and L; HS-HDZ, receiving HS and hydralazine (HDZ). Sixty days later, NS rats showed only slight albuminuria and renal damage or inflammation. In contrast, HS rats developed severe hypertension, marked glomerulosclerosis with interstitial expansion and renal infiltration by macrophages and angiotensin II-positive cells. The group treated with losartan had lowered blood pressure and a lack of albuminuria or renal injury. MMF provided similar protection without altering blood pressure, suggesting a nonhemodynamic effect, a hypothesis reinforced by the finding that HDZ lowered blood pressure without preventing renal injury. RESULTS: These results indicate that treatment with HS and NAME predisposes to the development of hypertension and renal injury upon salt overload, characterizing a new model of chronic nephropathy. CONCLUSION: The response to MMF or L, but not HDZ, suggests a key role for inflammatory rather than hemodynamic factors.
引用
收藏
页码:749 / 756
页数:8
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