GABA is a mediator of brain AT1 and AT2 receptor-mediated blood pressure responses

The nucleus tractus solitarius (NTS), paraventricular nucleus (PVN), and rostral ventrolateral medulla (RVLM) are the most targeted regions of central blood pressure control studies. Glutamate and gamma-aminobutyric acid (GABA) interact within these brain regions to modulate blood pressure. The brain renin-angiotensin system also participates in central blood pressure control. Angiotensin II increases blood pressure through the stimulation of angiotensin II type 1 (AT(1)) receptors within the PVN and RVLM and attenuates baroreceptor sensitivity, resulting in elevated blood pressure within the NTS. Angiotensin II type 2 (AT(2)) receptors in cardiovascular control centers in the brain also appear to be involved in blood pressure control and counteract AT(1) receptor-mediated effects. The current review is focused on the interaction of GABA with AT(1) and AT(2) receptors in the control of blood pressure within the RVLM, PVN and NTS. Within the NTS, GABA is released from local GABAergic interneurons that are stimulated by local AT(1) receptors and mediates a hypertensive response. In contrast, the local increase in GABA levels observed after AT(2) receptor stimulation within the RVLM, likely from GABAergic nerve endings originating in the caudal ventrolateral medulla, is important in the mediation of the hypotensive response. Preliminary results suggest that the hypertensive response to AT(1) receptor stimulation within the RVLM is associated with a reduction in GABA release. The current experimental evidence therefore indicates that GABA is an important mediator of brainstem responses to AT(1) and AT(2) receptor stimulation and that increased GABA release may play a role in hypertensive and hypotensive responses, depending on the site of action.