Angiotensin II increases GABA_B receptor expression in nucleus tractus solitarii of rats

Abstract

Increasing evidence indicates that both the angiotensin II (ANG II) and gamma-aminobutyric acid (GABA) systems play a very important role in the regulation of blood pressure (BP). However, there is little information concerning the interactions between these two systems in the nucleus tractus solitarii (NTS). In the present study, we examined the effects of ANG II on GABAA and GABAB receptor (GAR and GBR) expression in the NTS of Sprague-Dawley rats. The direct effect of ANG II on GBR expression was determined in neurons cultured from NTS. Treatment of neuronal cultures with ANG II (100 nM, 5 h) induced a twofold increase in GBR1 expression, as detected with real-time RT-PCR and Western blots, but had no effect on GBR2 or GAR expression. In electrophysiological experiments, perfusion of neuronal cultures with the GBR agonist baclofen decreased neuronal firing rate by 39% and 63% in neurons treated with either PBS (control) or ANG II, respectively, indicating that chronic ANG II treatment significantly enhanced the neuronal response to GBR activation. In contrast, ANG II had no significant effect on the inhibitory action of the GAR agonist muscimol. In whole animal studies, intracerebroventricular infusion of ANG II induced a sustained increase in mean BP and an elevation of GBR1 mRNA and protein levels in the NTS. These results indicate that ANG II stimulates GBR expression in NTS neurons, and this could contribute to the central nervous system actions of ANG II that result in dampening of baroreflexes and elevated BP in the central actions of ANG II.

GABAB receptors in the NTS mediate the inhibitory effect of trigeminal nociceptive inputs on parasympathetic reflex vasodilation in the rat masseter muscle

“…Evidence for this includes the fact that microinjection of the GABA A receptor agonist muscimol into the NTS markedly inhibited MBF increases evoked by cVN stimulation, as reported in our previous studies (12,13). Binding sites for GABA B receptors, as well as GABA A receptors, have been demonstrated to localize in the NTS (3,46). GABA B receptor agonist baclofen inhibits neuronal excitability in rat NTS neurons (7,23,42,48).…”

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

“…Actions in the central nervous system Blood pressure regulation NTS Baroreceptor reflex suppression through: AT receptor activation (Lucius et al, 1998;Paul et al, 2006) and inhibition of ACE2 activity (Xia et al, 2009). Increases expression of GABAb receptor that could contribute to baroreceptor reflex suppression (Yao et al, 2008). RVLM, PVN, SFO Increased sensitivity of cardiac sympathetic afferents via AT1 receptor (Epstein et al, 1970;Xia et al, 2009).…”

20-Hydroxyeicosatetraenoic Acid Is a Key Mediator of Angiotensin II–induced Apoptosis in Cardiac Myocytes

“…21 TaqMan probes specific for rat CYP4A1 were purchased from Applied Biosystems. Real-time RT-PCR was performed in an Applied Biosystems PRISM 7000 sequence detection system according to the protocol from the manufacturer.…”