Increased neuronal discharge in the RVLM of rats with chronic heart failure is mediated by AT1R

Abstract

It is well accepted that sympatho‐excitation is a hallmark of chronic heart failure (CHF). We have recently carried out a series of experiments documenting an important relationship between central AngII and sympatho‐excitation in animals with CHF. However direct neural recordings in the central nervous system of animals with CHF has not been carried out. In the current experiment we determined the spontaneous and AngII induced presympathetic neuronal activity in the RVLM of anesthetized sham and CHF rats. Experiments were performed on 15 sham rats and 18 CHF rats. A total of 39 and 51 neurons were recorded in sham and CHF rats, respectively. We found that (1) baseline neuronal discharge was higher in CHF rats (17.4 ± 1.2 spikes/sec, n = 51) than that in sham rats (9.6 ± 1.1 spikes/sec, n = 39; P < 0.05 vs CHF). (2) picoinjection of AngII into the vicinity of neurons significantly increased the firing rate in both sham (147 ± 11.4%, n = 37; P < 0.05 vs baseline) and CHF (189 ± 12.5%, n = 46; P < 0.05 vs baseline) rats. (3) Losartan significantly decreased the basal neuronal discharge in both sham (63 ± 12.6%, n = 37; P < 0.05 vs baseline) and CHF (32 ± 9.3%, n = 45; P < 0.05 vs baseline) rats. Losartan also completely abolished the AngII induced increased neuronal discharge. These results demonstrate the important role for AngII in the activity of presympathetic neurons in the RVLM of CHF rats. Together with our previous demonstration of an up regulation in AT1 receptors they suggest a pivotal role for central Ang II in the sympatho‐excitation of CHF. Supported by a SDG from AHA: 0635007N, NIH grants #PO‐1‐HL‐62222 and RO‐1‐HL‐38690.