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Chronic AT 1 receptor blockade normalizes NMDA‐mediated changes in renal sympathetic nerve activity from the paraventricular nucleus in heart failure
Author(s) -
Kleiber Allison,
Zheng Hong,
Patel Kaushik P.
Publication year - 2008
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.22.1_supplement.952.12
Subject(s) - medicine , nmda receptor , endocrinology , losartan , blockade , microinjection , receptor , heart failure , angiotensin ii
Increased renal sympathetic nerve activity (RSNA) after NMDA microinjection into the paraventricular nucleus (PVN) is potentiated in rats with chronic heart failure (HF), and normalized by exercise training, as is plasma angiotensin (Ang) II. We hypothesized that chronic Ang II receptor (AT 1 ) blockade would also normalize PVN NMDA‐mediated RSNA changes in rats with HF. We used four groups of rats: Sham+Vehicle (Veh); HF+Veh; Sham+Losartan (Los; 50 mg/kg/day in the drinking water, 3 wk); and HF+Los. HF was induced by coronary artery ligation. Cardiac function in both HF groups was similar after Los treatment. The highest dose of NMDA (200 pmol) injected into the PVN increased RSNA from baseline in the HF+Veh group 93±13%, significantly higher than in the Sham+Veh group (45±2%). The response in the HF+Los group (47±2%) was significantly lower than the HF+Veh group and not different from either Sham group. Furthermore, Los treatment in rats with HF normalized expression of the NR1 subunit of the NMDA receptor in the PVN. These data support our hypothesis that chronic AT 1 receptor blockade normalizes NMDA‐mediated changes in RSNA and NR1 expression within the PVN in rats with HF. (Support:NIH)