Angiotensin II enhances GABAB receptor-mediated responses and expression in nucleus tractus solitarii of rats

Abstract

Angiotensin II (ANG II) increases GABAB receptor expression in neuronal cultures from the nucleus tractus solitarii (NTS). In the present study, the chronic effects of ANG II on GABAB receptor expression and activity were examined in the NTS of Sprague-Dawley rats. Intracerebroventricular infusion of ANG II caused a significant elevation in blood pressure (BP) and an increase in GABAB receptor expression in the NTS. Conversely, chronic NG-nitro-l-arginine methyl ester (l-NAME) treatment also increased BP, but had no effect on GABAB receptor expression in the NTS. Next, we examined the BP response to the GABAB receptor agonist baclofen microinjected into the NTS of ANG II- or artificial cerebrospinal fluid (aCSF)-infused rats. NTS microinjection of baclofen increased BP in both groups of rats. However, the pressor response to baclofen was enhanced in ANG II-infused rats compared with aCSF-infused rats. In addition, bilateral microinjection of the GABAB receptor antagonist CGP-35348 into the NTS evoked a decrease in BP in both group of rats, and the depressor responses to CGP-35348 were enhanced in the ANG II-infused rats. In contrast, the pressor responses to the GABAA receptor agonist muscimol and the depressor responses to the GABAA receptor antagonist bicuculline were comparable between aCSF- and ANG II-infused rats. These results indicate that chronic ANG II infusion stimulates GABAB receptor expression and augments GABAB receptor-mediated responses in the NTS. This effect could contribute to the central nervous system actions of ANG II that result in dampening of baroreflexes and elevation in arterial BP.