Tags

Type your tag names separated by a space and hit enter

Chronic AT1 receptor blockade normalizes NMDA-mediated changes in renal sympathetic nerve activity and NR1 expression within the PVN in rats with heart failure.
Am J Physiol Heart Circ Physiol. 2010 May; 298(5):H1546-55.AJ

Abstract

Exercise training normalizes enhanced glutamatergic mechanisms within the paraventricular nucleus (PVN) concomitant with the normalization of increased plasma ANG II levels in rats with heart failure (HF). We tested whether ANG II type 1 (AT(1)) receptors are involved in the normalization of PVN glutamatergic mechanisms using chronic AT(1) receptor blockade with losartan (Los; 50 mg.kg(-1).day(-1) in drinking water for 3 wk). Left ventricular end-diastolic pressure was increased in both HF + vehicle (Veh) and HF + Los groups compared with sham-operated animals (Sham group), although it was significantly attenuated in the HF + Los group compared with the HF + Veh group. The effect of Los on cardiac function was similar to exercise training. At the highest dose of N-methyl-d-aspartate (NMDA; 200 pmol) injected into the PVN, the increase in renal sympathetic nerve activity was 93 +/- 13% in the HF + Veh group, which was significantly higher (P < 0.05) than the increase in the Sham + Veh (45 +/- 2%) and HF + Los (47 +/- 2%) groups. Relative NMDA receptor subunit NR(1) mRNA expression within the PVN was increased 120% in the HF + Veh group compared with the Sham + Veh group (P < 0.05) but was significantly attenuated in the HF + Los group compared with the HF + Veh group (P < 0.05). NR(1) protein expression increased 87% in the HF + Veh group compared with the Sham + Veh group but was significantly attenuated in the HF + Los group compared with the HF + Veh group (P < 0.05). Furthermore, in in vitro experiments using neuronal NG-108 cells, we found that ANG II treatment stimulated NR(1) protein expression and that Los significantly ameliorated the NR(1) expression induced by ANG II. These data are consistent with our hypothesis that chronic AT(1) receptor blockade normalizes glutamatergic mechanisms within the PVN in rats with HF.

Authors+Show Affiliations

Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, 985850 Nebraska Medical Center, Omaha, NE 68198-5850, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20173042

Citation

Kleiber, Allison C., et al. "Chronic AT1 Receptor Blockade Normalizes NMDA-mediated Changes in Renal Sympathetic Nerve Activity and NR1 Expression Within the PVN in Rats With Heart Failure." American Journal of Physiology. Heart and Circulatory Physiology, vol. 298, no. 5, 2010, pp. H1546-55.
Kleiber AC, Zheng H, Sharma NM, et al. Chronic AT1 receptor blockade normalizes NMDA-mediated changes in renal sympathetic nerve activity and NR1 expression within the PVN in rats with heart failure. Am J Physiol Heart Circ Physiol. 2010;298(5):H1546-55.
Kleiber, A. C., Zheng, H., Sharma, N. M., & Patel, K. P. (2010). Chronic AT1 receptor blockade normalizes NMDA-mediated changes in renal sympathetic nerve activity and NR1 expression within the PVN in rats with heart failure. American Journal of Physiology. Heart and Circulatory Physiology, 298(5), H1546-55. https://doi.org/10.1152/ajpheart.01006.2009
Kleiber AC, et al. Chronic AT1 Receptor Blockade Normalizes NMDA-mediated Changes in Renal Sympathetic Nerve Activity and NR1 Expression Within the PVN in Rats With Heart Failure. Am J Physiol Heart Circ Physiol. 2010;298(5):H1546-55. PubMed PMID: 20173042.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic AT1 receptor blockade normalizes NMDA-mediated changes in renal sympathetic nerve activity and NR1 expression within the PVN in rats with heart failure. AU - Kleiber,Allison C, AU - Zheng,Hong, AU - Sharma,Neeru M, AU - Patel,Kaushik P, Y1 - 2010/02/19/ PY - 2010/2/23/entrez PY - 2010/2/23/pubmed PY - 2010/5/19/medline SP - H1546 EP - 55 JF - American journal of physiology. Heart and circulatory physiology JO - Am J Physiol Heart Circ Physiol VL - 298 IS - 5 N2 - Exercise training normalizes enhanced glutamatergic mechanisms within the paraventricular nucleus (PVN) concomitant with the normalization of increased plasma ANG II levels in rats with heart failure (HF). We tested whether ANG II type 1 (AT(1)) receptors are involved in the normalization of PVN glutamatergic mechanisms using chronic AT(1) receptor blockade with losartan (Los; 50 mg.kg(-1).day(-1) in drinking water for 3 wk). Left ventricular end-diastolic pressure was increased in both HF + vehicle (Veh) and HF + Los groups compared with sham-operated animals (Sham group), although it was significantly attenuated in the HF + Los group compared with the HF + Veh group. The effect of Los on cardiac function was similar to exercise training. At the highest dose of N-methyl-d-aspartate (NMDA; 200 pmol) injected into the PVN, the increase in renal sympathetic nerve activity was 93 +/- 13% in the HF + Veh group, which was significantly higher (P < 0.05) than the increase in the Sham + Veh (45 +/- 2%) and HF + Los (47 +/- 2%) groups. Relative NMDA receptor subunit NR(1) mRNA expression within the PVN was increased 120% in the HF + Veh group compared with the Sham + Veh group (P < 0.05) but was significantly attenuated in the HF + Los group compared with the HF + Veh group (P < 0.05). NR(1) protein expression increased 87% in the HF + Veh group compared with the Sham + Veh group but was significantly attenuated in the HF + Los group compared with the HF + Veh group (P < 0.05). Furthermore, in in vitro experiments using neuronal NG-108 cells, we found that ANG II treatment stimulated NR(1) protein expression and that Los significantly ameliorated the NR(1) expression induced by ANG II. These data are consistent with our hypothesis that chronic AT(1) receptor blockade normalizes glutamatergic mechanisms within the PVN in rats with HF. SN - 1522-1539 UR - https://www.unboundmedicine.com/medline/citation/20173042/Chronic_AT1_receptor_blockade_normalizes_NMDA_mediated_changes_in_renal_sympathetic_nerve_activity_and_NR1_expression_within_the_PVN_in_rats_with_heart_failure_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.01006.2009?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -