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Telmisartan inhibits sympathetic nerve activity through the reduction of oxidative stress and release of GABA in RVLM of hypertensive rats
Author(s) -
Kishi Takuya,
Hirooka Yoshitaka,
Sunagawa Kenji
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.808.7
Subject(s) - rostral ventrolateral medulla , telmisartan , medicine , angiotensin ii , endocrinology , chemistry , angiotensin ii receptor type 1 , blood pressure , microinjection , angiotensin receptor , oxidative stress , renin–angiotensin system , heart rate
Background We have demonstrated that angiotensin II‐dependent reactive oxygen species (ROS) and ƒÁ‐amino butyric acid (GABA) in the rostral ventrolateral medulla (RVLM) play a major role in regulating sympathetic nerve activity (SNA) in hypertensive rats. The aim of this study was to determine whether oral administration of angiotensin II type 1 receptor (AT1R) blocker, telmisartan, decreases SNA via the reduction of ROS and release of GABA in the RVLM of hypertensive rats. Methods and Results We divided stroke‐prone spontaneously hypertensive rats (SHRSP), as a hypertensive model with enhanced SNA, into 2 groups, telmisartan‐group (TLM) and hydralazine‐group (HYD). Telemetered mean blood pressure (MBP) was reduced in both groups to a similar level. SNA and heart rate (HR) were significantly decreased in TLM, whereas increased in HYD. ROS in the RVLM were significantly lower in TLM than in HYD. The release of GABA measure by microdialysis was significantly higher in TLM than in HYD (15.1±0.7 vs 8.2±1.1 pmol/sample, n=5 for each, P<0.01). Microinjection of angiotensin II into the RVLM increased MBP and HR, and decreased GABA in the RVLM in HYD to a greater extent than in TLM. Conclusion Telmisartan decreases AT1R‐dependent ROS and increases GABA in the RVLM, thereby decreases SNA as well as blood pressure in SHRSP.