(PVN) has been repeatedly shown to increase arterial blood pressure (ABP), heart rate (HR), and sympathetic nerve activity (SNA), but the mechanism(s) that underlies this response has not been determined. Here, we tested whether full expression of the response requires activation of local ANG II AT 1 receptors. ABP, HR, and renal SNA responses to PVN microinjection of bicuculline methobromide (BIC; 0.1 nmol) were recorded before and after microinjection of vehicle (saline); losartan (or L-158809), to block local AT 1 receptors; or PD123319, to block AT2 receptors. After PVN microinjection of vehicle or PD123319 (10 nmol), BIC significantly (P Ͻ 0.05) increased mean arterial pressure (MAP), HR, and renal SNA. However, PVN microinjection of 2 and 20 nmol of losartan dose dependently reduced responses to PVN-injected BIC, with the 20-nmol dose nearly abolishing MAP (P Ͻ 0.005), HR (P Ͻ 0.05), and renal SNA (P Ͻ 0.005) responses. Another AT 1 receptor antagonist, L-158809 (10 nmol), produced similar effects. Neither losartan nor L-158809 altered baseline parameters. Responses to PVN injection of BIC were unchanged by losartan (20 nmol) given intravenously or into the PVN on the opposite side. MAP, HR, and renal SNA responses to PVN microinjection of L-glutamate (10 nmol) were unaffected by PVN injection of losartan (20 nmol), indicating that effects of losartan were not due to nonspecific depression of neuronal excitability. We conclude that pressor, tachycardic, and renal sympathoexcitatory responses to acute blockade of GABA-A receptors in the PVN depend on activation of local AT 1 receptors. bicuculline methobromide; angiotensin II; sympathetic nerve activity; arterial pressure; paraventricular nucleus ␥-AMINOBUTYRIC ACID (GABA) is the dominant inhibitory neurotransmitter in the mammalian brain. One region where GABA plays a key role in regulating cardiovascular function is the hypothalamic paraventricular nucleus (PVN). Here, GABAergic terminals account for nearly 50% of all synapses (10), and ongoing GABAergic activity results in a high level of functional inhibitory "tone." The latter is evident from numerous studies in which local GABA-A receptor blockade has been shown to produce dramatic increases in arterial blood pressure (ABP), heart rate (HR), and sympathetic nerve activity (SNA) in conscious and anesthetized rats (24,25,38,39).The fact that acute blockade of GABA-A receptors in the PVN produces prompt cardiovascular and autonomic responses indicates that a source of excitation is also present that is capable of increasing action potential discharge in PVN autonomic neurons. This is the case, because inhibition of neuronal discharge by GABA-A receptor activation results from membrane hyperpolarization caused by an increase in Cl Ϫ conductance through the GABA-A receptor channel (12). Consequently, GABA-A receptor blockade by itself only reduces membrane Cl Ϫ conductance and thus only removes GABA-mediated membrane hyperpolarization. In the absence of convergent excitation, GABA-A receptor blockade wou...