Biochemical and Biophysical Research Communications
Effects of tempol on renal angiotensinogen production in Dahl salt-sensitive rats
Section snippets
Materials and methods
The experimental protocol was approved by the Animal Care and Use Committees at Tulane University and Kagawa University. Male DS (200–220 g, Seac Yoshitomi, Fukuoka, Japan, N=34) were selected at random to receive HS (8% NaCl, Oriental Yeast, Osaka, Japan, N=27) or low salt diet (LS, 0.3% NaCl, Oriental Yeast, N=7) for 4 weeks. The HS group was subdivided into three subgroups to receive null (N=12), superoxide dismutase mimetic, tempol (T, 3 mmol/l, N=8, Sigma, Missouri, USA), or vasodilator,
Results
Temporal profile of systolic BP is depicted in Fig. 1A. Systolic BP levels were similar among the four groups at the beginning of protocol. Systolic BP was significantly increased in the DS + HS group compared to the DS + LS group (184 ± 7 mmHg vs. 107 ± 5 at 4-week). Tempol or hydralazine treatment equivalently attenuated the hypertension (128 ± 3 and 127 ± 5 at 4-week, respectively).
Plasma AGT levels are depicted in Fig. 2A. HS significantly suppressed plasma AGT levels. Tempol or hydralazine treatment
Discussion
While we recently reported that DS on HS have an inappropriate augmentation of intrarenal AGT and a failure to suppress intrarenal Ang II which may contribute to the development of hypertension in this strain [9], the mechanisms responsible for an inappropriate augmentation of intrarenal AGT by HS remain incompletely understood. Meanwhile, other groups recently reported that an augmented superoxide anion formation plays an important role in this animal model of hypertension [10], [11]. These
Acknowledgements
This work was supported by grants from the Institutional Development Award Program of the National Center for Research Resources, National Institute of Health (P20RR017659, H.K.), the Ministry of Education, Science and Culture of Japan (A.N.), and the Mitsui Life Social Welfare Foundation (Tokyo, Japan, A.N.). The polyclonal antibody against rat AGT was generously provided by Dr. Conrad Sernia (University of Queensland, Australia). The authors thank Dr. L. Gabriel Navar (Tulane University) for
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