Chronic AT1 receptor blockade normalizes NMDA-mediated changes in renal sympathetic nerve activity and NR1 expression within the PVN in rats with heart failure.

Kleiber AC, Zheng H, Sharma NM, Patel KP.

Previously it is known that glutamatergic mechanisms are normalized in the PVN on exercise treatment. Also plasma Ang II levels are normalized in the rats with heart failure. In this study the authors tested whether Ang II receptor AT1 was involved in this normalization effect. In order to test this the authors used AT1 receptor blocker losartan in drinking water for 3 wk. Left ventricular end-diastolic pressure was measured. It was increased in both the heart failure groups compared to the sham animals. Losartan had a similar effect like that of exercise training. When N-methyl-d-aspartate (NMDA) is injected in the PVN, it increased the RSNA in HF animals treated with losartan compared to other groups. NMDA receptor subunit NR(1) mRNA and protein expression levels were increased in the PVN in HF animals with losartan treatment. Invitro studies also confirmed the above finding. These data suggests that AT1 receptor are involved in the normalization of glutamatergic mechanisms in the PVN in heart failure rats.