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- Title
Chronic AT1 receptor blockade normalizes NR1 expression within the paraventricular nucleus (PVN) in rats with heart failure (HF).
- Authors
Kleiber, Allison; Hong Zheng; Patel, Kaushik P.
- Abstract
Exercise training (ExT) normalizes enhanced glutamatergic mechanisms within the PVN concomitant with normalization of increased plasma Angiotensin II (Ang II) levels in rats with HF. We tested whether Ang II activated AT1 receptors are involved in normalization of PVN glutamatergic mechanisms using four groups of rats: 1) Sham; 2) Sham+Losartan (Los; 50 mg/kg/day in the drinking water for 3 wk); 3) HF; and 4) HF+Los. HF was induced by left coronary artery ligation. Left ventricular end-diastolic pressure in both HF groups was significantly increased compared to Sham (5 mmHg±0.3) but was significantly attenuated in HF Los rats (16 mmH±3) compared to HF (25 mmHg±2). The effect of Los on cardiac function was similar to ExT. Relative NMDA receptor subunit NR] mRNA expression within the PVN was increased 63% in HF compared to sham but was significantly attenuated in the HF Los rats (28% decrease vs. Sham Los). NR1 protein expression increased 87% in HF compared to Sham but was significantly attenuated in HF Los rats (26% increase vs. Sham, p>0.05). NR1 protein expression was not changed in the supraoptic nucleus or lateral hypothalamus. These data support our hypothesis that ExT normalizes NR1 expression within the PVN in HF via an AT1 receptor mediated Ang II mechanism.
- Subjects
ANGIOTENSIN II; HEART failure; METHYL aspartate; MESSENGER RNA; LABORATORY rats
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA1267
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.6.a1267-b