Cellular and Molecular Neurobiology, Vol. 23, Nos. 4/5, October 2003 ( C  2003) Rostral Ventrolateral Medulla: An Integrative Site for Muscle Vasodilation during Defense-Alerting Reactions Sergio L. Cravo, 1,2 Olga S. Possas, 1 and Marcos L. Ferreira-Neto 1 Received July 15, 2002; accepted October 1, 2002 SUMMARY 1. Evidence gathered over the last 30 years has firmly established that the rostral ventrolateral medulla (RVLM) is a major vasomotor center in the brainstem, harboring sympathetic premotor neurons responsible for generating and maintaining basal vasomotor tone and resting levels of arterial blood pressure. Although the RVLM has been almost exclusively classified as a vasopressor area, in this report we review some evidence suggesting a prominent role of the RVLM in muscle vasodilation during defense-alerting responses. 2. Defense-alerting reactions are a broad class of behavior including flexion of a limb, fight/flight responses, apologies, etc. They comprise species-distinctive motor and neuroveg- etative adjustments. Cardiovascular responses include hypertension, tachycardia, visceral vasoconstriction, and muscle vasodilation. Since defense-alerting reactions generally in- volve intense motor activation, muscle vasodilation is regarded as a key feature of these responses. 3. In anesthetized or unanesthetized-decerebrate animals, natural or electrical stimu- lation of cutaneous and muscle afferents produced hypertension, tachycardia, and vasodi- lation restricted to the stimulated limb. 4. Unilateral inactivation of the RVLM contralateral to the stimulated limb abolished cardiovascular adjustments to stimulation of cutaneous and muscle afferents. Within the RVLM glutamatergic synapses mediate pressor responses, whereas GABAergic synapses mediates muscle vasodilation. 5. In urethane-anesthetized rats, electrical stimulation of the hypothalamus elicited hy- pertension, tachycardia, visceral vasoconstriction, and hindlimb vasodilation. The hindlimb vasodilation induced by hypothalamic stimulation is a complex response, involving reduc- tion of sympathetic vasoconstrictor tone, release of catecholamines by the adrenal medulla, and a still unknown system that may use nitric oxide as a mediator. 6. Blockade of glutamatergic transmission within the RVLM selectively blocks muscle vasodilation induced by hypothalamic stimulation. 7. The results obtained suggest that, besides its role in the generation and maintenance of the sympathetic vasoconstrictor drive, the RVLM is also critical for vasodilatory responses during defense reactions. The RVLM may contain several, distinctive mechanisms for muscle vasodilation. Anatomical and functional characterization of these pathways may represent a breakthrough in our understanding of cardiovascular control in normal and/or pathological conditions. KEY WORDS: muscle blood flow; rostral ventrolateral medulla; pain; hypertension; cate- cholamines; nitric oxide. 1 Department of Physiology, Universidade Federal de S˜ ao Paulo, 04023-060 S ˜ ao Paulo, SP, Brazil. 2 To whom correspondence should be addressed at Departamento de Fisiologia, Universidade Federal de S˜ ao Paulo, R. Botucatu, 862, 04023-060 S ˜ ao Paulo, SP, Brazil; e-mail: sldcravo@fcr.epm.br 579 0272-4340/03/1000-0579/0 C  2003 Plenum Publishing Corporation