Abstract-Angiotensin II type 1 (AT 1 ) receptors are located on pressor neurons in the rostral ventrolateral medulla, and their activation results in an increase in arterial pressure. However, the normal role of these AT 1 receptors in cardiovascular regulation is unknown. In this study, we tested the hypothesis that these receptors mediate synaptic excitation of rostral ventrolateral medullary pressor neurons in response to activation of the hypothalamic paraventricular nucleus. In anesthetized rats, microinjections of the ␥-aminobutyric acid receptor antagonist bicuculline were made into the paraventricular nucleus; this injection causes activation of the nucleus as a consequence of disinhibition. The pressor and sympathoexcitatory responses evoked by paraventricular nucleus activation were significantly reduced (by Ϸ40% to 50%) after microinjection of the specific AT 1 receptor antagonists losartan or L-158,809 into the rostral ventrolateral medulla on the ipsilateral, but not contralateral, side. These responses were reduced to a similar degree after microinjections of the neuroinhibitory compound muscimol into the ipsilateral, but not contralateral, rostral ventrolateral medulla. However, bilateral microinjections of the glutamate receptor antagonist kynurenic acid into the rostral ventrolateral medulla had no effect on the responses evoked from the paraventricular nucleus. Conversely, bilateral microinjections of kynurenic acid into the rostral ventrolateral medulla virtually abolished the somatosympathoexcitatory reflex, whereas bilateral microinjections of losartan or L-158,809 had no effect on this reflex. The results indicate that excitatory synaptic inputs to pressor neurons in the rostral ventrolateral medulla arising from activation of the paraventricular nucleus are mediated predominantly by AT 1 receptors. (Hypertension. 1999;34:1301-1307.)Key Words: angiotensin II Ⅲ blood pressure Ⅲ brain Ⅲ receptors, glutamate Ⅲ bicuculline Ⅲ blood vessels I t is well established that the rostral part of the ventrolateral medulla (RVLM) contains a group of spinally projecting sympathoexcitatory neurons that play a crucial role in the tonic and phasic regulation of sympathetic vasomotor activity and arterial blood pressure (for reviews see References 1 and 2). These neurons are a site of convergence of central pathways subserving many cardiovascular reflexes as well as responses evoked from higher brain regions. 1,2 Numerous studies have demonstrated that glutamate and ␥-aminobutyric acid (GABA) receptors play a major role in the synaptic regulation of RVLM sympathoexcitatory neurons. 1,2 There is also evidence, however, indicating that angiotensin (Ang) receptors may also play a role in the synaptic regulation of these neurons. First, studies using in vitro autoradiography have shown that there is a high density of Ang receptors in the RVLM of several mammalian species, including humans (for review see Reference 3). These receptors are predominantly Ang II type 1 (AT 1 ) receptors, and their location corresponds...