Interaction between Ang II and GABA systems in NTS: Central resetting of blood pressure regulation

Abstract

There is little information concerning the interactions between Ang II and GABA systems in the NTS. Our previous studies, using gene microarrays, demonstrated that the GABA-B receptor (GBR) expression was increased following treatment of cultured NTS neurons with Ang II. In the present study, we examined the effects of Ang II on GBR expression in the NTS of SD rats. Ang II or saline control was infused subcutaneously for 2 weeks with osmotic minipumps. Ang II infusion induced a sustained increase in mean BP. GBR mRNA levels in NTS brain tissue were detected with real-time PCR showing GBR1 mRNA levels in the NTS were significantly increased in Ang II-infused rats. To rule out the possibility that the alterations of GBR expression observed in the above experiment is a result of the elevated BP, we examined the effect of Ang II on GBR expression in neurons cultured from NTS. Ang II treatment (100 nM, 5 hrs) induced a 2-fold increase in GBR mRNA levels. In addition, Superfusion of baclofen decreased the neuronal firing rate by 39% and 63% respectively in control and Ang II-treated neurons. In summary, these experiments indicate that Ang II stimulates GBR expression, consequently enhances GABAergic neurotransmission in the NTS. This enhanced GABAergic neurotransmission may lead to dampening of baroreflexes and consequently central resetting of long-term blood pressure regulation to a higher level in Ang II-related hypertension. Supported by AHA grant 0635050N