RESUMO
Microinjection of angiotensin II into the nucleus tractus solitarii attenuates the baroreceptor reflex-mediated bradycardia by inhibiting both vagal and cardiac sympathetic components. However, it is not known whether the baroreflex modulation of other sympathetic outputs (i.e., noncardiac) also are inhibited by exogenous angiotensin II (ANG II) in nucleus tractus solitarii (NTS). In this study, we determined whether there was a difference in the baroreflex sensitivity of sympathetic outflows at the thoracic and lumbar levels of the sympathetic chain following exogenous delivery of ANG II into the NTS. Experiments were performed in two types of in situ arterially perfused decerebrate rat preparations. Sympathetic nerve activity was recorded from the inferior cardiac nerve, the midthoracic sympathetic chain, or the lower thoracic-lumbar sympathetic chain. Increases in perfusion pressure produced a reflex bradycardia and sympathoinhibition. Microinjection of ANG II (500 fmol) into the NTS attenuated the reflex bradycardia (57% attenuation, P < 0.01) and sympathoinhibition of both the inferior cardiac nerve (26% attenuation, P < 0.05) and midthoracic sympathetic chain (37% attenuation, P < 0.05) but not the lower thoracic-lumbar chain (P = 0.56). We conclude that ANG II in the nucleus tractus solitarii selectively inhibits baroreflex responses in specific sympathetic outflows, possibly dependent on the target organ innervated.
Assuntos
Angiotensina II/farmacologia , Barorreflexo/fisiologia , Núcleo Solitário/fisiologia , Sistema Nervoso Simpático/fisiologia , Vasoconstritores/farmacologia , Angiotensina II/administração & dosagem , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Interpretação Estatística de Dados , Eletrofisiologia , Agonistas GABAérgicos/farmacologia , Coração/inervação , Ácidos Isonicotínicos/farmacologia , Masculino , Microinjeções , Ratos , Ratos Wistar , Vasoconstritores/administração & dosagemRESUMO
AIM: Neurons in the rostral ventrolateral medulla (RVLM) that project directly to sympathetic preganglionic neurons in the spinal cord play a critical role in maintaining tonic activity in sympathetic vasomotor nerves. Intracellular recordings in vivo from putative RVLM presympathetic neurons have demonstrated that under resting conditions these neurons display an irregular tonic firing rate, and also receive both excitatory and inhibitory synaptic inputs. This paper will briefly review some recent findings on the role of glutamate, GABA and angiotensin II (Ang II) receptors in maintaining the tonic activity of RVLM presympathetic neurons. RESULTS: Based on these findings, the following hypotheses will be discussed: (1) RVLM neurons receive tonic glutamatergic excitatory inputs, which originate from both medullary and supramedullary sources; (2) at least some neurons that project to and tonically inhibit RVLM presympathetic neurons are themselves tonically inhibited by GABAergic inputs originating from neurons in the caudalmost part of the ventrolateral medulla (caudal pressor area); (3) under normal conditions, Ang II receptors in the RVLM do not contribute significantly to the tonic activity of RVLM presympathetic neurons, but may do so in abnormal conditions such as heart failure or neurogenic hypertension; (4) RVLM presympathetic neurons maintain a significant level of tonic resting activity even when glutamate, GABA and Ang II receptors on the neurons are completely blocked. Under these conditions, the tonic activity is a consequence either of the intrinsic membrane properties of the neurons (autoactivity) or of synaptic inputs mediated by receptors other than glutamate, GABA or Ang II receptors. CONCLUSION: The current evidence indicates that the resting activity of RVLM presympathetic neurons is determined by the balance of powerful tonic excitatory and inhibitory synaptic inputs. Ang II receptors also contribute to the raised resting activity of these neurons in some pathological conditions.
Assuntos
Angiotensina II/fisiologia , Bulbo/fisiologia , Receptores de Angiotensina/fisiologia , Receptores de GABA/fisiologia , Receptores de Glutamato/fisiologia , Sistema Vasomotor/fisiologia , Animais , Bicuculina/farmacologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Rim/inervação , Rim/fisiologia , Ácido Cinurênico/farmacologia , Tono Muscular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Neurônios/fisiologia , Pressorreceptores/fisiologia , Ratos , Receptores de GABA/efeitos dos fármacosRESUMO
1. Sympathetic vasomotor nerves play a major role in determining the level of arterial blood pressure and the distribution of cardiac output. The present review will discuss briefly the central regulatory mechanisms that control the sympathetic outflow to the cardiovascular system in the short and long term. 2. In the short term, the sympathetic vasomotor outflow is regulated by: (i) homeostatic feedback mechanisms, such as the baroreceptor or chemoreceptor reflexes; or (ii) feed-forward mechanisms that evoke cardiovascular changes as part of more complex behavioural responses. 3. The essential central pathways that subserve the baroreceptor reflex and, to a lesser extent, other cardiovascular reflexes, have been identified by studies in both anaesthetized and conscious animals. A critical component of these pathways is a group of neurons in the rostral ventrolateral medulla that project directly to the spinal sympathetic outflow and that receive inputs from both peripheral receptors and higher centres in the brain. 4. Much less is known about the central pathways subserving feed-forward or 'central command' responses, such as the cardiovascular changes that occur during exercise or that are evoked by a threatening or alerting stimulus. However, recent evidence indicates that the dorsomedial hypothalamic nucleus is a critical component of the pathways mediating the cardiovascular response to an acute alerting stimulus. 5. Long-term sustained changes in sympathetic vasomotor activity occur under both physiological conditions (e.g. a change in salt intake) and pathophysiological conditions (e.g. heart failure). There is evidence that the paraventricular nucleus in the hypothalamus is a critical component of the pathways mediating these changes. 6. Understanding the central mechanisms involved in the long-term regulation of sympathetic activity and blood pressure is a major challenge for the future. As a working hypothesis, a model is presented of the postulated central mechanisms that result in sustained changes in sympathetic vasomotor activity that are evoked by different types of chronic stimulation.
Assuntos
Sistema Cardiovascular/inervação , Animais , Sistema Cardiovascular/fisiopatologia , Retroalimentação , Homeostase/fisiologia , Humanos , Sistema Nervoso Simpático/fisiologiaRESUMO
The aim of this study was to investigate the expression of the alpha2-adrenergic receptors in the adrenal medulla, and to examine the mechanism by which clonidine and related drugs inhibit acetylcholine (ACh)-induced whole-cell currents in adrenal chromaffin cells. Reverse transcription-polymerase chain reaction (RT-PCR) performed on punches of rat adrenal medulla demonstrated expression of mRNA for the 2A-, alpha2B- and alpha2C-adrenergic receptors. Similar experiments conducted with tissue punches obtained from the adrenal cortex did not reveal expression of these receptor subtypes. Whole-cell currents were recorded in isolated chromaffin cells using the perforated-patch configuration. ACh (50 microM) evoked inward currents with a peak amplitude of 117.8+/-9.3 pA (n = 45; Vhol = -60 mV). The currents were inhibited in a dose-dependent manner (0.5-50 microM) by clonidine, UK 14,304 and rilmenidine (agonists of alpha2/imidazoline receptors), as well as by SKF 86466 and efaroxan (antagonists). Adrenaline and noradrenaline (50-100 microM) had no significant effect. Thus, although the adrenal medulla expresses mRNA for the alpha2-adrenergic receptors, the lack of agonist-antagonist specificity observed in our whole-cell recordings (in the absence of intracellular dialysis) provides additional evidence against the possibility that these inhibitory effects are mediated by classical alpha2 or imidazoline receptor interactions.
Assuntos
Acetilcolina/farmacologia , Glândulas Suprarrenais/fisiologia , Células Cromafins/fisiologia , Receptores Adrenérgicos alfa/fisiologia , Receptores de Droga/fisiologia , Glândulas Suprarrenais/efeitos dos fármacos , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Catecolaminas/biossíntese , Células Cromafins/efeitos dos fármacos , Condutividade Elétrica , Eletrofisiologia , Enzimas/genética , Enzimas/metabolismo , Feminino , Expressão Gênica , Receptores de Imidazolinas , Ligantes , Masculino , Ratos , Ratos Wistar , Receptores Adrenérgicos alfa/genética , Receptores de Droga/agonistas , Receptores de Droga/antagonistas & inibidoresRESUMO
Physiological and anatomic methods were used to determine whether neurons in the rostral ventrolateral medulla (RVLM), nucleus tractus solitarius (NTS), or hypothalamic paraventricular nucleus (PVN) mediate the cardiovascular response evoked from the dorsomedial hypothalamic nucleus (DMH), which is believed to play a key role in mediating responses to stress. In urethane-anesthetized rats, activation of neurons in the DMH by microinjection of bicuculline resulted in a large increase in arterial pressure, heart rate, and renal sympathetic nerve activity. The pressor and sympathoexcitatory responses, but not the tachycardic response, were greatly reduced after bilateral muscimol injections into the RVLM even when baseline arterial pressure was maintained at a constant level. These responses were not reduced by muscimol injections into the PVN or NTS. Retrograde tracing experiments identified many neurons in the DMH that projected directly to the RVLM. The results indicate that the vasomotor and cardiac components of the response evoked from the DMH are mediated by pathways that are dependent and independent, respectively, of neurons in the RVLM.
Assuntos
Sistema Cardiovascular/inervação , Núcleo Hipotalâmico Dorsomedial/fisiologia , Bulbo/fisiologia , Vias Neurais/fisiologia , Antagonistas Adrenérgicos beta/administração & dosagem , Animais , Bicuculina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Núcleo Hipotalâmico Dorsomedial/citologia , Núcleo Hipotalâmico Dorsomedial/efeitos dos fármacos , Agonistas GABAérgicos/administração & dosagem , Antagonistas GABAérgicos/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Injeções Intravenosas , Rim/inervação , Masculino , Bulbo/citologia , Bulbo/efeitos dos fármacos , Microinjeções , Microesferas , Muscimol/administração & dosagem , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Núcleo Hipotalâmico Paraventricular/citologia , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/fisiologia , Ratos , Ratos Sprague-Dawley , Núcleo Solitário/citologia , Núcleo Solitário/efeitos dos fármacos , Núcleo Solitário/fisiologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiologiaRESUMO
1. The present review discusses the mechanisms that maintain the tonic activity of presympathetic cardiovascular neurons in the rostral part of the ventrolateral medulla. 2. Experimental evidence is reviewed that indicates that these neurons receive both tonic excitatory and tonic inhibitory synaptic inputs. The former appear to be mediated, at least in part, by glutamate receptors and the latter appear to be mediated by GABA receptors. 3. There is also evidence that these neurons have the capacity to generate action potentials in the absence of synaptic inputs. However, at present, there is not clear evidence that such an intrinsic pacemaker-like mechanism contributes to the tonic activity of these neurons under normal resting conditions. 4. These neurons are also chemosensitive and this may contribute to their tonic activation under conditions of hypoxia or hypercapnia.
Assuntos
Sistema Cardiovascular/inervação , Bulbo/fisiologia , Neurônios/fisiologia , Sistema Nervoso Simpático/fisiologia , Potenciais de Ação , Animais , Células Quimiorreceptoras/fisiologia , Humanos , Bulbo/citologia , Rede Nervosa/fisiologia , Sistema Nervoso Simpático/citologia , Sinapses/fisiologia , Ácido gama-Aminobutírico/fisiologiaRESUMO
Hypotension produces a reflex increase in the activity of sympathetic vasomotor and cardiac nerves. It is believed that the reflex sympathoexcitation is due largely to disinhibition of sympathoexcitatory neurons in the rostral ventrolateral medulla, but it is possible that it may also be mediated by excitatory inputs from interneurons that are activated by a fall in blood pressure. The aim of this study in conscious rabbits was to identify and map neurons with properties that are characteristic of interneurons conveying excitatory inputs to the rostral ventrolateral medullary pressor region in response to hypotension. In a preliminary operation, a retrogradely-transported tracer, fluorescent-labelled microspheres, was injected into the functionally-identified pressor region in the rostral ventrolateral medulla. After a waiting period of at least one week, a moderate hypotension (decrease in arterial pressure of approximately 20 mmHg) was induced in conscious rabbits for 60 min by the continuous infusion of sodium nitroprusside. In confirmation of a previous study from our laboratory, [Li and Dampney (1994) Neuroscience 61, 613634] hypotension resulted in the expression of Fos (the protein product of c-fos, a marker of neuronal activation) in many neurons in several distinct regions in the brainstem and hypothalamus. Some of these regions (nucleus tractus solitarius, area postrema, caudal and intermediate ventrolateral medulla, parabrachial complex in the pons, and paraventricular nucleus in the hypothalamus) also contained large numbers of retrogradely-labelled cells. Approximately 10% of the Fos-positive neurons in the nucleus tractus solitarius, and 15-20% of Fos-positive neurons in the caudal and intermediate ventrolateral medulla were also retrogradely-labelled from the rostral ventrolateral medullary pressor region. In other brain regions, very few double-labelled neurons were found. In previous studies from our laboratory, we have determined the distribution of neurons in the brainstem that project to the rostral ventrolateral medullary pressor region and that are also activated by hypertension [Polson et al. (1995) Neuroscience 67, 107-123] or by hypoxia. [Hirooka et al. (1997) Neuroscience 80, 1209-1224] Comparison of the present results with those from these previous studies indicate that although hypotension and hypoxia both elicit powerful reflex sympathoexcitatory responses, the central pathways subserving these effects in conscious animals are fundamentally different. Hypoxia activates rostral ventrolateral medullary sympathoexcitatory neurons mainly via a major direct excitatory projection from the nucleus tractus solitarius, as well as from the Kölliker-Fuse nucleus in the pons, while in contrast the activation of these neurons in response to hypotension appears to be due mainly to disinhibition, mediated via inhibitory interneurons. In addition, however, inputs originating from excitatory interneurons in the nucleus tractus solitarius and caudal and intermediate parts of the ventrolateral medulla appear to contribute to the hypotension-evoked activation of sympathoexcitatory neurons in the rostral ventrolateral medulla.
Assuntos
Pressão Sanguínea/fisiologia , Mapeamento Encefálico , Tronco Encefálico/fisiologia , Hipotensão/fisiopatologia , Hipotálamo/fisiologia , Bulbo/fisiologia , Bulbo/fisiopatologia , Neurônios/fisiologia , Animais , Transporte Axonal , Tronco Encefálico/fisiopatologia , Corantes Fluorescentes , Hipotálamo/fisiopatologia , Interneurônios/fisiologia , Microesferas , CoelhosRESUMO
Previous studies in anaesthetized animals have shown that the hypoxia-induced increase in sympathetic vasomotor activity is largely dependent on synaptic excitation of sympathoexcitatory pressor neurons in the rostral part of the ventrolateral medulla. The primary aim of this study was to determine, in conscious rabbits, the distribution of neurons within the brain that have properties characteristic of interneurons conveying excitatory inputs to the rostral ventrolateral medullary pressor region in response to systemic hypoxia. In a preliminary operation, a retrogradely-transported tracer, fluorescent-labelled microspheres, was injected into the physiologically-identified pressor region in the rostral ventrolateral medulla. After a waiting period of one to two weeks, the conscious rabbits were subjected to moderate hypoxia (induced by breathing 10% O2 in N2) for a period of 60 min. Control groups of animals were exposed to room air or to mild hypoxia (12% O2 in N2). Moderate hypoxia resulted in a modest hypertension of approximately 15 mmHg, and in the expression of Fos (a marker of neuronal activation) in many neurons in the nucleus tractus solitarius, the rostral, intermediate and caudal parts of the ventrolateral medulla, the Kölliker-Fuse nucleus, locus coeruleus, subcoeruleus and A5 area in the pons as well as in several midbrain and forebrain regions, including the periaqueductal grey in the midbrain and the paraventricular, supraoptic and arcuate nuclei in the hypothalamus. Fos expression was also observed in these regions in rabbits subjected to mild hypoxia or normoxia, but it was much reduced compared to rabbits subjected to moderate hypoxia. Approximately half of the neurons in the ventrolateral medulla, 27% of neurons in the nucleus tractus solitarius, and 49-81% of neurons in the locus coeruleus, sub-coeruleus and A5 area that expressed Fos following moderate hypoxia were also immunoreactive for tyrosine hydroxylase, and were therefore catecholamine cells. Approximately half of the neurons in the nucleus tractus solitarius and two-thirds of neurons in the Kölliker-Fuse nucleus that expressed Fos following moderate hypoxia were retrogradely labelled from the rostral ventrolateral medullary pressor region. Similarly, approximately one quarter of Fos-positive cells in the caudal and intermediate ventrolateral medulla were retrogradely labelled, but very few Fos-positive/retrogradely-labelled cells were found in other pontomedullary or suprapontine brain regions. The results indicate that systemic hypoxia results in activation of neurons in several discrete nuclei in the brainstem and forebrain, including neurons in all the major pontomedullary catecholamine cell groups. However, neurons that are activated by systemic hypoxia and that also project to the rostral ventrolateral medullary pressor region are virtually confined to the lower brainstem, primarily in the nucleus tractus solitarius and Kölliker-Fuse nucleus and to a lesser extent the caudal/intermediate ventrolateral medulla. In a previous study from our laboratory, we determined the distribution of neurons in the brainstem that are activated by hypertension and that also project to the rostral ventrolateral medullary pressor region. [Polson et al. (1995) Neuroscience 67, 107-123]. Comparison of the present results with those from this previous study indicates that the hypoxia-activated neurons in the nucleus tractus solitarius and Kölliker-Fuse nucleus that project to the rostral ventrolateral medulla are likely to be interneurons conveying excitatory chemoreceptor signals, while those in the caudal/intermediate ventrolateral medulla are likely to be mainly interneurons conveying inhibitory baroreceptor signals, activated by the rise in arterial blood pressure associated with the hypoxia-induced hypertension.
Assuntos
Pressão Sanguínea , Mapeamento Encefálico , Expressão Gênica , Genes fos , Frequência Cardíaca , Hipóxia/fisiopatologia , Bulbo/fisiologia , Neurônios/fisiologia , Ponte/fisiologia , Animais , Feminino , Imuno-Histoquímica , Masculino , Proteínas Proto-Oncogênicas c-fos/biossíntese , CoelhosRESUMO
We have previously shown [Li and Dampney (1994) Neuroscience 61, 613-634] that periods of sustained hypertension and hypotension each induces a distinctive and reproducible pattern of neuronal expression of Fos (a marker of neuronal activation) in specific regions of the brainstem and forebrain of conscious rabbits. The aim of this study was to determine the contribution of afferent inputs from arterial baroreceptors to the activation of neurons in these various brain regions that is caused by a sustained change in arterial pressure. Experiments were carried out on rabbits in which the carotid sinus and aortic depressor nerves were cut in a preliminary operation. Following a recovery period of seven to 10 days, a moderate hypertension or hypotension (increase or decrease in arterial pressure of 20-30 mmHg) was induced in conscious barodenervated rabbits for 60 min by the continuous infusion of phenylephrine or sodium nitroprusside, respectively. In control experiments, barodenervated rabbits were subjected to the identical procedures except that they were infused with the vehicle solution alone. Compared with the effects seen in barointact rabbits, [Li and Dampney (1994) Neuroscience 61, 613-634] the number of neurons that expressed Fos in response to hypertension was reduced by approximately 90% in the nucleus of the solitary tract and in the caudal and intermediate parts of the ventrolateral medulla. In supramedullary regions, baroreceptor denervation resulted in a reduction of approximately 60% in hypertension-induced Fos expression in the central nucleus of the amygdala and in the bed nucleus of the stria terminalis, but no significant reduction in the parabrachial complex in the pons. Following hypotension, the number of neurons that expressed Fos in barodenervated rabbits, compared with barointact rabbits, [Li and Dampney (1994) Neuroscience 61, 613-634] was reduced by approximately 90% in the nucleus of the solitary tract, area postrema, and caudal, intermediate and rostral parts of the ventrolateral medulla. Baroreceptor denervation also resulted in a similar large reduction in hypotension-induced Fos expression in many supramedullary regions (locus coeruleus, midbrain periaqueductal grey, hypothalamic paraventricular nucleus, and in the central nucleus of the amygdala and the bed nucleus of the stria terminalis in the basal forebrain). In the supraoptic nucleus, hypotension-induced Fos expression in barodenervated rabbits was reduced by 75% compared to barointact animals, but was still significantly greater than in control animals. There was also a high level of Fos expression, much greater than in control animals, in the circumventricular organs surrounding the third ventricle (subfornical organ and organum vasculosum lamina terminalis). The results indicate that in conscious rabbits the activation of neurons that occurs in several discrete regions at all levels of the brain following a sustained change in arterial pressure is largely dependent upon inputs from arterial baroreceptors, with the exception of neurons in the circumventricular organs surrounding the third ventricle that are activated by sustained hypotension. The latter group of neurons are known to project to vasopressin-secreting neurons in the supraoptic nucleus, and may therefore via this pathway trigger the hypotension-induced release of vasopressin that occurs in the absence of baroreceptor inputs.
Assuntos
Química Encefálica/fisiologia , Hipertensão/metabolismo , Hipotensão/metabolismo , Proteínas Proto-Oncogênicas c-fos/biossíntese , Nó Sinoatrial/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Denervação , Feminino , Hipertensão/induzido quimicamente , Hipotensão/induzido quimicamente , Imuno-Histoquímica , Masculino , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Pressorreceptores/fisiologia , Coelhos , Vasoconstritores/farmacologiaRESUMO
OBJECTIVE: It has been shown that nitric oxide (NO) plays an important role in the central control of arterial pressure and sympathetic nerve activity. The aim of this study was to determine whether NO can regulate sympathetic nerve activity by an action on pressor neurons within the rostral part of the ventrolateral medulla (VLM). DESIGN AND METHODS: Experiments were performed on anaesthetized rabbits with denervated arterial and cardiopulmonary baroreceptors. The mean arterial pressure (MAP), heart rate and renal sympathetic nerve activity were measured. Microinjections of the NO donors sodium nitroprusside (SNP, 4-50 nmol) and S-nitroso-glutathione (10 nmol), the NO precursor L-arginine (50 nmol) and the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 50 nmol), were made into the functionally identified pressor region in the rostral VLM. The effects of SNP were also determined before and after injection of 5 nmol methylene blue into the same area. In control experiments, injections of D-arginine (50 nmol) and D-NAME (50 nmol), which are the inactive isomers of L-arginine and L-NAME, respectively, were also made into the functionally identified pressor region in the rostral VLM. RESULTS: Microinjections of SNP into the rostral VLM pressor region produced a dose-dependent increase in mean arterial pressure and renal sympathetic nerve activity. At the highest dose of 50 nmol, the increase in MAP was 26 +/- 5 mmHg (P < 0.001) and the sympathetic nerve activity was 53 +/- 5% (P < 0.001). These effects were abolished following methylene blue injection into the same region. Injection of 10 nmol S-nitroso-glutathione also produced increases in MAP (15 +/- 2 mmHg, P < 0.001) and in renal sympathetic nerve activity (28 +/- 2%, P < 0.001). Microinjections of L- or D-arginine resulted in very small depressor responses, but had no significant effect on renal sympathetic nerve activity. Microinjections of L-NAME, but not of D-NAME, caused significant decreases in MAP (19 +/- 1 mmHg, P < 0.001) and in sympathetic nerve activity (30 +/- 3%, P < 0.001). CONCLUSIONS: The results indicate that, in the anaesthetized rabbit with denervated baroreceptors, NO has a pressor and sympathoexcitatory action in the rostral VLM, which is mediated by a cyclic GMP-dependent mechanism. Second, endogenous NO may modulate sympathetic activity tonically, by a direct or indirect action on sympathoexcitatory neurons within the rostral VLM.
Assuntos
Pressão Sanguínea/fisiologia , Bulbo/fisiologia , Óxido Nítrico/fisiologia , Sistema Nervoso Simpático/fisiologia , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Glutationa/análogos & derivados , Glutationa/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Rim/inervação , Masculino , Bulbo/efeitos dos fármacos , Microinjeções , NG-Nitroarginina Metil Éster/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroprussiato/farmacologia , Compostos Nitrosos/farmacologia , Coelhos , S-Nitrosoglutationa , Sistema Nervoso Simpático/efeitos dos fármacosRESUMO
Previous studies in anaesthetized animals have shown that the baroreflex control of sympathetic vasomotor activity is mediated to a large extent by inhibitory inputs to sympathoexcitatory pressor neurons in the rostral part of the ventrolateral medulla. The aim of this study was to determine, in conscious rabbits, the distribution of neurons within the brain that have two properties characteristic of interneurons conveying baroreceptor signals to the rostral ventrolateral medulla: (i) they are activated by an increase in arterial pressure; and (ii) they project specifically to the rostral ventrolateral medulla pressor region. In a preliminary operation, an injection of the retrogradely transported tracer, fluorescent-labelled microspheres, was made into the physiologically identified pressor region in the rostral ventrolateral medulla. After a waiting period of one to eight weeks, hypertension was produced in the conscious rabbit by continuous intravenous infusion of phenylephrine at a rate sufficient to increase arterial pressure by approximately 20 mmHg, maintained for a period of 60 min. A control group of animals was infused with the vehicle solution alone. In confirmation of our previous study, hypertension produced by phenylephrine resulted in the neuronal expression of Fos (a marker of neuronal activation) in the nucleus of the solitary tract, area postrema, the intermediate and caudal parts of the ventrolateral medulla parabrachial complex, and in the central nucleus of the amygdala. Approximately 50% of the Fos-immunoreactive neurons in both the caudal and intermediate parts of the ventrolateral medulla were also retrogradely labelled from the rostral ventrolateral medulla pressor region; such double-labelled neurons were confined to a discrete longitudinal column located just ventrolateral to the nucleus ambiguus. Significant numbers of double-labelled neurons were also found in the nucleus of the solitary tract and area postrema, although these represented a much lower proportion (13-16%) of the total number of Fos-immunoreactive neurons in these regions. In the parabrachial complex, Fos-immunoreactive and retrogradely labelled neurons were largely separate populations, while in the amygdala they were entirely separate populations. In the control group of rabbits, virtually no double-labelled neurons were found in any of these regions. The results indicate that putative baroreceptor interneurons that project to the pressor region of the rostral ventrolateral medulla are virtually confined to the lower brainstem. In particular, they support the results of previous studies in anaesthetized animals indicating that neurons in the intermediate and caudal ventrolateral medulla convey baroreceptor signals to the rostral ventrolateral medulla pressor region, and extend them by demonstrating the precise anatomical distribution of these neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Pressão Sanguínea/fisiologia , Expressão Gênica/fisiologia , Genes fos , Hipertensão/fisiopatologia , Interneurônios/metabolismo , Bulbo/metabolismo , Animais , Feminino , Imuno-Histoquímica , Masculino , Bulbo/citologia , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Perfusão , Fenilefrina/farmacologia , Coelhos , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Prolonged stimulation of many neurons results in the expression of the immediate early gene c-fos, which in turn cause the production of the protein Fos, whose presence in a cell can be detected by immunocytochemistry. This method has been used in both conscious and anaesthetized animals to identify central neurons involved in the baroreceptor reflex. In this paper we review the factors that can influence c-fos expression, with particular emphasis on the effects of different anaesthetic agents. We conclude that the c-fos method of functional mapping, when applied carefully and critically, is a very useful method of identifying central neurons that are activated by cardiovascular stimuli in conscious animals. Anaesthetic agents can significantly alter c-fos expression, and this effect differs greatly according to the type of anaesthetic used.
Assuntos
Barorreflexo/genética , Barorreflexo/fisiologia , Mapeamento Encefálico/métodos , Sistema Nervoso Central/fisiologia , Genes fos , Anestesia , Animais , Expressão Gênica , Hipertensão/fisiopatologia , Bulbo/fisiologia , Vias Neurais/fisiologia , Fatores de TempoRESUMO
Excitatory amino acid (EAA) receptors in the rostral part of the ventrolateral medulla (VLM) have been shown to mediate pressor responses elicited by stimulation of various peripheral afferent fibers as well as other central nuclei. This study tested the hypothesis that these receptors are a critical component in the central pathway mediating the powerful pressor response that is produced by stimulation of a group of neurons within a circumscribed region in the rostral dorsomedial medulla (RDM). In anesthetized rabbits, the pressor response elicited by unilateral microinjection of glutamate into this RDM region was measured before and after injection of kynurenic acid (Kyn), a broad-spectrum EAA receptor antagonist, into the physiologically identified pressor region of either the ipsilateral or contralateral rostral VLM. The pressor response to RDM stimulation was greatly reduced (to 24 +/- 4% of control) 5-10 min after injection of Kyn (but not the vehicle solution) into the ipsilateral rostral VLM; this response returned completely to its control value within 30-60 min after Kyn injection. By contrast, after Kyn injection into the contralateral rostral VLM, the pressor response to RDM stimulation was not affected (106 +/- 15% of control). The results indicate that the descending pressor pathway from the RDM to the spinal cord is mediated by EAA receptors in the rostral VLM pressor region. Furthermore, the pathway from the RDM to the rostral VLM is predominantly, if not exclusively, ipsilateral.
Assuntos
Pressão Sanguínea/fisiologia , Bulbo/fisiologia , Receptores de Aminoácido/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Estimulação Elétrica , Feminino , Ácido Cinurênico/farmacologia , Masculino , Bulbo/efeitos dos fármacos , Coelhos , Receptores de Aminoácido/antagonistas & inibidores , Nervo Isquiático/fisiologiaRESUMO
Microinjections of the excitatory amino acid L-glutamate were made into the rostral ventrolateral medulla (RVLM) of anesthetised cats, to map the sites at which selective stimulation of cell bodies elicited a significant antinociceptive response (> or = 15% inhibition of the increase in L7 ventral root activity reflexly evoked by stimulation of C-fiber afferents). Antinociceptive sites were largely confined to the RVLM subregion ventromedial to the retrofacial nucleus, extending from the caudal pole of the facial nucleus to the level approximately 2.5 mm more caudal. Increases in arterial pressure were also elicited from some sites in the RVLM, but these were mainly lateral to the antinociceptive sites. In a second series of experiments, rhodamine labeled microspheres or cholera toxin B-gold (CTB-gold) were injected into the dorsal horn of the L7 segment. In three of these experiments in which the injection sites were restricted to the dorsal horn, retrogradely labeled cells in the caudal pons and medulla were virtually all within either the nucleus raphe magnus or the RVLM. Furthermore, the labeled cells in the RVLM were virtually confined to a discrete group located just ventromedial to the retrofacial nucleus, i.e. within the antinociceptive region as mapped by glutamate microinjection. The results of the present study indicate that antinociceptive effects are elicited by stimulation of a subregion in the RVLM, which is located medial to the pressor region. Further, the antinociceptive effects may be mediated, at least in part, by cells projecting directly to the dorsal horn in the spinal cord.
Assuntos
Bulbo/anatomia & histologia , Bulbo/fisiologia , Inibição Neural/fisiologia , Nociceptores/fisiologia , Animais , Mapeamento Encefálico , Gatos , Toxina da Cólera/farmacologia , Vias Eferentes/anatomia & histologia , Vias Eferentes/fisiologia , Glutamatos/farmacologia , Ácido Glutâmico , Coloide de Ouro , Microesferas , Rodaminas , Medula Espinal/fisiologiaRESUMO
The rostral ventrolateral medulla (RVLM) contains sympathoexcitatory neurons that exert a powerful control over the sympathetic outflow to the cardiovascular system. In the cat there is a concentration of such neurons (but not neurons subserving other functions) within a narrow longitudinal column in the RVLM termed the subretrofacial (SRF) nucleus. Furthermore, it has been suggested that there are subgroups of cells, located at different rostrocaudal levels of the SRF nucleus, that preferentially or exclusively control different vascular beds (e.g. in the kidney and hindlimb). The aim of this study was to map quantitatively the rostrocaudal distribution within the nucleus of different cell types, defined according to morphological and/or chemical criteria, and to correlate this with the regional vasomotor effects (in hindlimb and kidney) evoked by stimulation of SRF cells at the corresponding rostrocaudal levels. SRF cells were highly heterogeneous with respect to both their morphology and chemical properties. They varied greatly in size (equivalent diameter ranging from 10-40 microns) as well as in shape and orientation. An immunohistochemical examination using the avidin-biotin procedure revealed that many SRF cells (estimated 57% of all SRF cells) were immunoreactive for tyrosine hydroxylase (TH, a marker of catecholamine cells). In addition, there were SRF cells immunoreactive for neuropeptide Y (NPY, 11% of total), enkephalin (ENK, 16% of total), and serotonin (5HT, 10% of total), but not for substance P, galanin or somatostatin. Different cell types, defined according to their morphology and/or chemical properties, were unevenly distributed throughout the nucleus. In the most caudal part of the SRF nucleus, virtually all cells were TH-positive, and the large majority (estimated 80%) were NPY-positive, suggesting that many cells at this level contained both TH and NPY. In contrast, in the most rostral part of the SRF nucleus, only 30% of cells were TH-positive, and no NPY-positive cells were observed. Both 5HT- and ENK-positive cells were found throughout the rostrocaudal extent of the nucleus, but predominantly within its rostral part. Furthermore, TH-positive cells in the rostral SRF nucleus were on average significantly larger (mean equivalent diameter 18-43% greater) than TH/NPY-positive cells in the caudal part of the nucleus, but smaller than 5HT- or ENK-positive cells at the same level. Overall, rostral cells (regardless of their chemical type) were larger than caudal cells within the SRF nucleus (mean equivalent diameter 13-28% greater).(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Bulbo/metabolismo , Neurotransmissores/metabolismo , Anestesia , Animais , Mapeamento Encefálico , Gatos , Encefalinas/metabolismo , Galanina , Imuno-Histoquímica , Bulbo/anatomia & histologia , Bulbo/citologia , Microinjeções , Neuropeptídeo Y/metabolismo , Peptídeos/metabolismo , Serotonina/metabolismo , Somatostatina/metabolismo , Substância P/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
We examined the vasomotor and respiratory effects of angiotensin II microinjection into the rabbit ventrolateral medulla (VLM). Angiotensin II in the rostral and caudal VLM increased and decreased arterial pressure, respectively, but had no effect on phrenic nerve activity. In contrast, L-glutamate injections in the same areas altered both arterial pressure and phrenic nerve activity. The results suggest that angiotensin II may activate specifically vasomotor neurons but not respiratory neurons in the VLM.