GABA-A receptor blockade in the hypothalamic paraventricular nucleus (PVN) elicits a characteristic increase in arterial blood pressure (ABP), heart rate (HR) and sympathetic nerve activity (SNA). However, the specific neural mechanism(s) that underlies this response has not been determined. Here, we tested the hypothesis that activation of local angiotensin II (ANG II) AT₁ receptors is required for full expression of the response to PVN GABA-A receptor blockade. ABP, HR and renal SNA responses to unilateral PVN microinjection of bicuculline methobromide (BIC, 0.1 nmol) were recorded before and after microinjection of either vehicle (saline), Losartan (or L-158809) to block local AT₁ receptors or PD123319 to block AT₂ receptors. Following vehicle injections, BIC significantly (P<0.05) increased mean arterial pressure (MAP), HR and renal SNA. However, following PVN microinjection of 2 and 20 nmol doses of Losartan, responses to PVN microinjected BIC were reduced in a dose-dependent manner, with the 20 nmol dose nearly abolishing MAP (P<0.005), HR (P<0.05) and renal SNA (P< 0.005) responses. Another AT₁ receptor antagonist L-158809 (10 nmol) produced similar effects. AT₁ receptor antagonist effects were maximal within ~20 minutes and responses to microinjected BIC returned to near control levels within ~120 minutes. Neither Losartan nor L-158809 altered baseline parameters. Responses to BIC injection into the PVN were unchanged by either Losartan (20 nmol) given i.v. 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 non-specific depression of neuronal excitability. Finally, responses to BIC microinjected into PVN were unaffected by prior injection of the AT₂ receptor antagonist PD123319 (10 nmol). We conclude that pressor, tachycardic and renal sympathoexcitatory responses to acute blockade of GABA-A receptors in the PVN depend on activation of local AT₁ receptors.