期刊
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
卷 290, 期 6, 页码 R1616-R1625出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00615.2005
关键词
kidney disease; nitric oxide; mitochondria; oxidative stress; hypertension
类别
Mitochondrial dysfunction is associated with cardiovascular damage; however, data on a possible association with kidney damage are scarce. Here, we aimed at investigating whether 1) kidney impairment is related to mitochondrial dysfunction; and 2) ANG II blockade, compared with Ca2+ channel blockade, can reverse potential mitochondrial changes in hypertension. Eight-week-old male spontaneously hypertensive rats (SHR) received water containing losartan (40 mg center dot kg(-1) center dot day(-1), SHR + Los), amlodipine (3 mg center dot kg(-1) center dot day(-1), SHR + Amlo), or no additions (SHR) for 6 mo. Wistar-Kyoto rats (WKY) were normotensive controls. Glomerular and tubulointerstitial damage, systolic blood pressure, and proteinuria were higher, and creatinine clearance was lower in SHR vs. SHR + Los and WKY. In SHR + Amlo, blood pressure was similar to WKY, kidney function was similar to SHR, and renal lesions were lower than in SHR, but higher than in SHR + Los. In kidney mitochondria from SHR and SHR + Amlo, membrane potential, nitric oxide synthase, manganese-superoxide dismutase and cytochrome oxidase activities, and uncoupling protein-2 content were lower than in SHR + Los and WKY. In SHR and SHR + Amlo, mitochondrial H2O2 production was higher than in SHR + Los and WKY. Renal glutathione content was lower in SHR + Amlo relative to SHR, SHR + Los, and WKY. In SHR and SHR + Amlo, glutathione was relatively more oxidized than in SHR + Los and WKY. Tubulointerstitial alpha-smooth muscle actin labeling was inversely related to manganese-superoxide dismutase activity and uncoupling protein-2 content. These findings suggest that oxidant stress is associated with renal mitochondrial dysfunction in SHR. The mitochondrial-antioxidant actions of losartan may be an additional or alternative way to explain some of the beneficial effects of AT(1)-receptor antagonists.
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