Ionotropic glutamate receptors in the rostral ventrolateral medulla mediate sympathetic responses to acute stress in conscious rabbits Dmitry N. Mayorov * , Geoffrey A. Head Baker Medical Research Institute, P.O. Box 6492, St. Kilda Rd. Central, Melbourne, Victoria 8008, Australia Abstract In conscious, chronically instrumented rabbits (n = 7), airjet stress evoked increases in arterial pressure (AP) and renal sympathetic nerve activity (RSNA), which were greatest in the first 2 min ( + 10 mm Hg and + 127%, respectively), but then rapidly reached a stable level ( + 7 mm Hg and + 37%, respectively). Bilateral microinjection into the rostral ventrolateral medulla (RVLM) of an ionotropic excitatory amino acid (EAA) receptor antagonist kynurenate (10 nmol/200 nl) did not affect resting AP and RSNA, but reduced their initial peak responses to airjet by 80% and 52%, respectively, without altering the stable levels of these responses. By contrast, bilateral microinfusion of glutamate (2 nmol/20 nl/min) into the RVLM increased resting AP by 13 mm Hg, but did not alter the RSNA and AP responses to airjet stress. These results suggest that the RVLM is an essential site for conveying excitatory environmental influences to the sympathetic nervous system in conscious rabbits. The EAA receptors are critically important in initiating the pressor and sympathoexcitatory responses to acute emotional stress, but play relatively little role in the maintenance of these responses. D 2002 Elsevier Science B.V. All rights reserved. Keywords: RVLM; Stress; EAA; Arterial pressure; Sympathetic activity The pressor region of the rostral ventrolateral medulla (RVLM) is critical in the maintenance and reflex control of sympathetic activity (Dampney and Moon, 1980; Granata et al., 1983). The RVLM is also the anatomical site of con- vergence of excitatory inputs from higher brain structures, such as the hypothalamus, midbrain periaqueductal gray and amygdala, primarily mediating the autonomic response to environmental (emotional) stressors (Dampney et al., 1987; Koepke and DiBona, 1986). Furthermore, the RVLM con- stitutes the largest subset of brain neurons, which provide a dual input to the cardiac and adrenal sympathetic pregan- glionic neurons and most likely function as command premotor neurons in circumstances where parallel sympa- thetic processing occurs, such as in the fight-or-flight response (Jansen et al., 1995). However, the relative impor- tance of synaptic transmission within the RVLM in media- ting cardiovascular responses to alerting environmental stimuli remains elusive. Experiments in anesthetized ani- mals utilizing stimulation of descending pressor pathways to the RVLM, which were likely to convey stress-related information, have produced conflicting results. Microinjec- tions of an ionotropic excitatory amino acid (EAA) receptor antagonist kynurenic acid into the RVLM attenuated the pressor responses evoked from the hypothalamic sites in some studies (Bauer et al., 1989; Coote et al., 1998; Sun and Guyenet, 1986), but had little effect in others (Kiely and Gordon, 1994; Tagawa and Dampney, 1999). In any case, contribution of the RVLM to defense-type cardiovascular reactions in conscious animals may be quite different from those in anesthetized models, in which only one excitatory input to the RVLM is typically stimulated. In order to explore the role of the RVLM in the autonomic response to excitatory environmental stimuli, in particular to psychoemotional stress, it is critical to perform experiments in conscious animals. In this study, we determined, in conscious rabbits, whether blockade of EAA receptors in the RVLM with kynurenic acid inhibits the renal sympa- thoexcitatory response to acute stress evoked by a jet of air. We also used local microinfusion of glutamate to determine whether neuronal excitation in the RVLM augments the magnitude of the circulatory response to acute stress. We delivered the drugs via a recently developed bilateral micro- injecting system, which allowed us to selectively modulate neuronal activity in highly circumscribed regions of the ventrolateral medulla in conscious rabbits (Mayorov and Head, 2001). The experiments were performed in seven conscious rabbits of either sex, weighing 2.7–3.0 kg, and bred and 1566-0702/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. PII:S1566-0702(02)00024-3 * Corresponding author. Fax: +61-3-85321100. E-mail address: Dmitry.Mayorov@baker.edu.au (D.N. Mayorov). www.elsevier.com/locate/autneu Autonomic Neuroscience: Basic and Clinical 98 (2002) 20 – 23