Importância da região AV3V para as respostas pressoras produzidas pela ativação de áreas bulbares

Abstract

Cardiovascular responses are integrated at different levels of the central nervous system (CNS). Particularly the hypothalamus and brainstem areas are involved in the control of autonomic responses and among them the cardiovascular responses. Different areas in the brainstem, like the nucleus tract solitarii (NTS), the rostroventrolateral medulla (RVLM), caudoventrolateral medulla (CVLM) and the nucleus ambigus are important to cardiovascular control. These areas of the brainstem that control the cardiovascular system receive information from receptors present in different parts of the body, specially the pressoreceptors and chemoreceptores and control the activity of the autonomic efferents. Injection of the excitatory amino acid glutamate into the NTS in anesthetized rats produces depressor response and bradycardia like barorreflex activation. Differently, in unanesthetized rats, injection of the glutamate into the NTS produces pressor response and bradycardia, similar to chemoreflex activation. The neuropeptide substance P may act as neurotransmitter or neuromodulator of differents cardiovascular reflexes and when injected into the NTS produces pressor response. The RVLM is the main site of sympathetic output to the intermediolateral cell column of the spinal cord. Injection of glutamate into the RVLM increases sympathetic activity and induces pressor response. Hypotalamic areas are also involved in the control of cardiovascular responses. For example, electrolytic lesions in the paraventricular nucleus of the hypothalamus (PVN), reduce the pressor response to chemoreflex activation with potassium cyanide (KCN) iv Another hypothalamic area important for cardiovascular control is the anteroventral third ventricle (AV3V) region. Electrolytic lesion of the AV3V region reduces the cardiovascular responses produced by central colinergic and angiotensinergic activation and abolish many forms of the experimental hypertension in animals. In the present study, in unanesthetized rats, we investigated the effects of acute (1 day) and cronic (15 days) AV3V lesions in the pressor responses produced by NTS activation with injection of the excitatory amino acid glutamate and substance P or injection of glutamate into the RVLM. The responses to activation of the baroreflex and chemoreflex were also tested. Rats with sham or electrolytic lesions of the AV3V region and stainless steel cannulas implanted into the NTS or RVLM were used. Mean arterial pressure (MAP) and heart rate (HR) were recorded in unanesthetized rats. A polyethylene tubing was inserted into the abdominal aorta through the femoral artery on day before the experiments. A second polyethylene tubing was inserted in the femoral vein for the baroreflex and chemoreflex tests. The central injections were made using 5 µl Hamilton syringes. The volume of the central injections into the NTS and RVLM was 100 nl. In sham rats, the injection of glutamate (5 nmol) into the NTS produce pressor response (28 ± 3 mmHg). The same dose of glutamate in acute AV3V-lesioned rats produce hypotension (-26 ± 8 mmHg) in the first day after lesion or did not modify the MAP (2 ± 8 mmHg) fifteen days after AV3V lesion. The bradycardic responses produced by injection of the glutamate into the NTS in acute (-65 ± 23 bpm) or cronic (-90 ± 29 bpm) AV3Vlesioned rats were not different from the bradycardic responses produced by glutamate into the NTS in sham-lesioned rats (-76 ± 13 e -90 ± 15 bpm). Differently, the pressor response produced by injection of substance P (0,5 e 1 nmol) into the NTS in acute (16 ± 2 and 20 ± 2 mmHg, respectively) or chronic AV3V-lesioned rats (18 ± 1 and 20 ± 1 mmHg) were not different from the pressor responses produced by the same doses of substance P into the NTS in acute (20 ± 5 and 22 ± 3 mmHg) or chronic sham rats (19 ± 3 and 25 ± 3 mmHg). The tachycardic responses produced by injection of substance P into the NTS in acute (54 ± 15 and 71 ± 15 bpm) and chronic AV3V-lesioned rats (70 ± 11 and 66 ± 11 bpm) were also not different from the tachycardic responses produced by substance P into the NTS in acute (75 ± 14 and 72 ± 12 bpm) or chronic sham rats (53 ± 16 e 84 ± 7 bpm). The pressor responses produced by injections of glutamate (1, 5 and 10 nmol) into the RVLM in acute (9 ± 4, 39 ± 6 e 37 ± 4 mmHg, respectively) or chronic AV3V-lesioned rats (13 ± 6, 39 ± 4 and 43 ± 4 mmHg, respectively) were significantly reduced compared to the pressor responses of the same doses of glutamate into the RVLM in acute (33 ± 5, 54 ± 3 and 56 ± 8 mmHg, respectively) or chronic sham rats (29 ± 3, 50 ± 2 and 58 ± 3 mmHg, respectively). Glutamate into the RVLM in acute or chronic sham or AV3V lesioned rats produced no significant change in the heart rate. The baroreflex responses produced by iv phenylephrine (5 µg/kg of body weight), sodium nitroprussiade (30 µg/kg of body weight), or the responses produced by chemoreflex activation with iv injection of potassium cyanide (20 and 40 µg/rato) were not modified by acute or chronic AV3V lesion. The results show the importance of the AV3V region for the cardiovascular responses dependent on the activation of the sympathetic nervous system and specially the pressor responses to glutamatergic activation in the NTS and RVLM. The integrity of the AV3V region is important for the pressor responses to injection of glutamate into the NTS and into the RVLM, but not for the pressor response to injection of substance P into the NTS, which suggests that the AV3V lesion does not non specifically affect any pressor mechanism. The AV3V lesions do not modify the baro and chemoreflex responses, suggesting that the sympatoexcitatory responses to chemoreflex activation do not depend unique and exclusively on glutamatergic neurotransmission in the NTS and RVLM.