RESUMEN
Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.
Asunto(s)
Volumen Sanguíneo/fisiología , Catecolaminas/fisiología , Líquido Extracelular/fisiología , Bulbo Raquídeo/fisiología , Equilibrio Hidroelectrolítico/fisiología , Vías Aferentes/fisiología , Aorta/inervación , Fenómenos Fisiológicos Cardiovasculares , Arterias Carótidas/inervación , Humanos , Riñón/metabolismo , Vías Nerviosas/fisiología , Neuronas/fisiología , Sodio/metabolismoRESUMEN
Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.
Asunto(s)
Humanos , Volumen Sanguíneo/fisiología , Catecolaminas/fisiología , Líquido Extracelular/fisiología , Bulbo Raquídeo/fisiología , Equilibrio Hidroelectrolítico/fisiología , Vías Aferentes/fisiología , Aorta/inervación , Fenómenos Fisiológicos Cardiovasculares , Arterias Carótidas/inervación , Riñón/metabolismo , Vías Nerviosas/fisiología , Neuronas/fisiología , Sodio/metabolismoRESUMEN
We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means +/- SEM) 2.47 +/- 0.08 to 2.14 +/- 0.07; conscious, 7 days: from 2.85 +/- 0.13 to 2.07 +/- 0.33; anesthetized, 2 days: from 3.00 +/- 0.09 to 1.83 +/- 0.25 and anesthetized, 7 days: from 3.56 +/- 0.11 to 1.53 +/- 0.10 mmHg mL-1 min-1) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 +/- 4.5 to 96 +/- 4; anesthetized: from 118 +/- 1.5 to 104 +/- 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension.
Asunto(s)
Gasto Cardíaco/fisiología , Hipertensión/fisiopatología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Sistema Nervioso Simpático/fisiopatología , Resistencia Vascular/fisiología , Animales , Gasto Cardíaco/efectos de los fármacos , Modelos Animales de Enfermedad , Inhibidores Enzimáticos , Hipertensión/inducido químicamente , Masculino , NG-Nitroarginina Metil Éster , Ratas , Ratas Wistar , Resistencia Vascular/efectos de los fármacosRESUMEN
We evaluated the hemodynamic pattern and the contribution of the sympathetic nervous system in conscious and anesthetized (1.4 g/kg urethane, iv) Wistar rats with L-NAME-induced hypertension (20 mg/kg daily). The basal hemodynamic profile was similar for hypertensive animals, conscious (N = 12) or anesthetized (N = 12) treated with L-NAME for 2 or 7 days: increase of total peripheral resistance associated with a decrease of cardiac output (CO) compared to normotensive animals, conscious (N = 14) or anesthetized (N = 14). Sympathetic blockade with hexamethonium essentially caused a decrease in total peripheral resistance in hypertensive animals (conscious, 2 days: from (means ± SEM) 2.47 ± 0.08 to 2.14 ± 0.07; conscious, 7 days: from 2.85 ± 0.13 to 2.07 ± 0.33; anesthetized, 2 days: from 3.00 ± 0.09 to 1.83 ± 0.25 and anesthetized, 7 days: from 3.56 ± 0.11 to 1.53 ± 0.10 mmHg mL-1 min-1) with no change in CO in either group. However, in the normotensive group a fall in CO (conscious: from 125 ± 4.5 to 96 ± 4; anesthetized: from 118 ± 1.5 to 104 ± 5.5 mL/min) was observed. The responses after hexamethonium were more prominent in the hypertensive anesthetized group. However, no difference was observed between conscious and anesthetized normotensive rats in response to sympathetic blockade. The present study shows that the vasoconstriction in response to L-NAME was mediated by the sympathetic drive. The sympathetic tone plays an important role in the initiation and maintenance of hypertension.
Asunto(s)
Animales , Masculino , Ratas , Gasto Cardíaco/fisiología , Hipertensión/fisiopatología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Sistema Nervioso Simpático/fisiología , Resistencia Vascular/fisiología , Gasto Cardíaco/efectos de los fármacos , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Hipertensión/inducido químicamente , NG-Nitroarginina Metil Éster/farmacología , Ratas Wistar , Resistencia Vascular/efectos de los fármacosRESUMEN
The rostral ventrolateral medulla (RVLM) contains neurons involved in tonic and reflex control of arterial pressure. We describe the effects of gamma-aminobutyric acid (GABA) and anesthetics injected into the RVLM of conscious and urethane (1.2 g/kg, iv) anesthetized Wistar rats (300-350 g). In conscious rats, bilateral microinjection of GABA (50 nmol/200 nl) induced a small but significant decrease in blood pressure (from 130 ± 3.6 to 110 ± 5.6 mmHg, N = 7). A similar response was observed with sodium pentobarbital microinjection (24 nmol/200 nl). However, in the same animals, the fall in blood pressure induced by GABA (from 121 ± 8.9 to 76 ± 8.8 mmHg, N = 7) or pentobarbital (from 118 ± 4.5 to 57 ± 11.3 mmHg, N = 6) was significantly increased after urethane anesthesia. In contrast, there was no difference between conscious (from 117 ± 4.1 to 92 ± 5.9 mmHg, N = 7) and anesthetized rats (from 123 ± 6.9 to 87 ± 8.7 mmHg, N = 7) when lidocaine (34 nmol/200 nl) was microinjected into the RVLM. The heart rate variations were not consistent and only eventually reached significance in conscious or anesthetized rats. The right position of pipettes was confirmed by histology and glutamate microinjection into the RVLM. These findings suggest that in conscious animals the RVLM, in association with the other sympathetic premotor neurons, is responsible for the maintenance of sympathetic vasomotor tone during bilateral RVLM inhibition. Activity of one or more of these premotor neurons outside the RVLM can compensate for the effects of RVLM inhibition. In addition, the effects of lidocaine suggest that fibers passing through the RVLM are involved in the maintenance of blood pressure in conscious animals during RVLM inhibition
Asunto(s)
Animales , Masculino , Ratas , Anestésicos Intravenosos , Presión Sanguínea , Ácido gamma-Aminobutírico , Frecuencia Cardíaca , Bulbo Raquídeo , Uretano , Anestésicos Locales , Sedación Consciente , Moduladores del GABA , Ácido gamma-Aminobutírico , Lidocaína , Microinyecciones , Pentobarbital , Ratas WistarRESUMEN
The rostral ventrolateral medulla (RVLM) contains neurons involved in tonic and reflex control of arterial pressure. We describe the effects of gamma-aminobutyric acid (GABA) and anesthetics injected into the RVLM of conscious and urethane (1.2 g/kg, iv) anesthetized Wistar rats (300-350 g). In conscious rats, bilateral microinjection of GABA (50 nmol/200 nl) induced a small but significant decrease in blood pressure (from 130 +/- 3.6 to 110 +/- 5.6 mmHg, N = 7). A similar response was observed with sodium pentobarbital microinjection (24 nmol/200 nl). However, in the same animals, the fall in blood pressure induced by GABA (from 121 +/- 8.9 to 76 +/- 8.8 mmHg, N = 7) or pentobarbital (from 118 +/- 4.5 to 57 +/- 11.3 mmHg, N = 6) was significantly increased after urethane anesthesia. In contrast, there was no difference between conscious (from 117 +/- 4.1 to 92 +/- 5.9 mmHg, N = 7) and anesthetized rats (from 123 +/- 6.9 to 87 +/- 8.7 mmHg, N = 7) when lidocaine (34 nmol/200 nl) was microinjected into the RVLM. The heart rate variations were not consistent and only eventually reached significance in conscious or anesthetized rats. The right position of pipettes was confirmed by histology and glutamate microinjection into the RVLM. These findings suggest that in conscious animals the RVLM, in association with the other sympathetic premotor neurons, is responsible for the maintenance of sympathetic vasomotor tone during bilateral RVLM inhibition. Activity of one or more of these premotor neurons outside the RVLM can compensate for the effects of RVLM inhibition. In addition, the effects of lidocaine suggest that fibers passing through the RVLM are involved in the maintenance of blood pressure in conscious animals during RVLM inhibition.
Asunto(s)
Anestésicos Intravenosos/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Bulbo Raquídeo/efectos de los fármacos , Uretano/farmacología , Ácido gamma-Aminobutírico/farmacología , Anestésicos Locales/administración & dosificación , Anestésicos Locales/farmacología , Animales , Sedación Consciente , Moduladores del GABA/administración & dosificación , Moduladores del GABA/farmacología , Lidocaína/administración & dosificación , Lidocaína/farmacología , Masculino , Microinyecciones , Pentobarbital/administración & dosificación , Pentobarbital/farmacología , Ratas , Ratas Wistar , Ácido gamma-Aminobutírico/administración & dosificaciónRESUMEN
Brain pathways controlling arterial pressure are distributed throughout the neuraxis and are organized in topographically selective networks. In this brief review, we will focus on the medulla oblongata. The nucleus tractus solitarius (NTS) is the primary site of cardiorespiratory reflex integration. It is well accepted that lesions or other perturbations in the NTS can result in elevations of arterial pressure (AP), with many of the associated features so commonly found in humans. However, recent studies have shown 2 distinct subpopulations of neurons within the NTS that can influence AP in opposite ways. Commissural NTS neurons located on the midline may contribute to maintenance of hypertension in spontaneously hypertensive rats (SHR), because small lesions in this area result in a very significant reduction in AP. Also involved in this blood pressure regulation network are 2 distinct regions of the ventrolateral medulla: caudal (CVLM) and rostral (RVLM). Neurons in CVLM are thought to receive baroreceptor input and to relay rostrally to control the activity of the RVLM. Projections from CVLM to RVLM are inhibitory, and a lack of their activity may contribute to development of hypertension. The RVLM is critical to the tonic and reflexive regulation of AP. In different experimental models of hypertension, RVLM neurons receive significantly more excitatory inputs. This results in enhanced sympathetic neuronal activity, which is essential for the development and maintenance of the hypertension.
Asunto(s)
Hipertensión/fisiopatología , Bulbo Raquídeo/fisiopatología , Animales , Modelos Animales de Enfermedad , Humanos , Vías Nerviosas/fisiopatologíaRESUMEN
Stimulation of cutaneous and muscle afferents induces several cardiovascular adjustments such as hypertension, tachycardia, and muscle vasodilation. Although previous studies have demonstrated that the rostral ventrolateral medulla (RVL) mediates sympathoexcitation and pressor responses to sciatic nerve stimulation (SNS), whether it also mediates blood flow adjustments remains unclear. Therefore, in the present study, we examined the role of the RVL in the vasodilation induced by SNS and the possible neurotransmitters involved. In Urethane-anesthetized, paralyzed, and artificially ventilated rats, SNS (square pulses, 1 ms, 20 Hz, 800--1200 microA, 10 s) produced increases in blood pressure, heart rate, blood flow, and vascular conductance of the stimulated limb. Unilateral microinjection of kainic acid (2 nmol/100 nl) into the RVL contralateral to the stimulated limb abolished cardiovascular adjustments to SNS. Unilateral microinjections of kynurenic acid (2 nmol/100 nl) selectively abolished the pressor response to SNS, whereas bicuculline (400 pmol/100 nl) abolished the increases in blood flow without changing the pressor response. These results suggest that glutamatergic synapses within the RVL mediate pressor responses, whereas GABAergic synapses may mediate the vasodilation to SNS.
Asunto(s)
Ácido Glutámico/fisiología , Hemodinámica/fisiología , Bulbo Raquídeo/fisiología , Ácido gamma-Aminobutírico/fisiología , Animales , Bicuculina/administración & dosificación , Bicuculina/farmacología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Estimulación Eléctrica , Lateralidad Funcional , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Hemodinámica/efectos de los fármacos , Miembro Posterior/irrigación sanguínea , Ácido Kaínico/administración & dosificación , Ácido Kaínico/farmacología , Ácido Quinurénico/administración & dosificación , Ácido Quinurénico/farmacología , Masculino , Bulbo Raquídeo/efectos de los fármacos , Microinyecciones , Músculo Esquelético/inervación , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Nervio Ciático/fisiología , Piel/inervación , Sistema Nervioso Simpático/fisiología , Vasodilatación/fisiologíaRESUMEN
The role of baroreceptors, cardiopulmonary receptors, and renal nerves in the cardiovascular adjustments to volume expansion (VE) with 4% Ficoll (Pharmacia; 1% body wt, 0.4 ml/min) were studied in urethan-anesthetized rats. In control animals, VE produced a transitory increase in mean arterial pressure (MAP), which peaked at 10 min (17 +/- 4 mmHg) and increases in renal (128 +/- 6 and 169 +/- 19% of baseline at 10 and 40 min, respectively) and hindlimb vascular conductance (143 +/- 6 and 150 +/- 10%). These cardiovascular adjustments to VE were unaffected by bilateral vagotomy. After sinoaortic denervation, the increase in MAP induced by VE was greater than in control rats (30 +/- 4 mmHg). However, renal vasodilation in response to VE was blocked, whereas hindlimb vasodilation was similar to that observed in control rats. After unilateral renal denervation (ipsilateral to flow recording), the initial renal vasodilation was blocked. However, 40 min after VE, a significant renal vasodilation (125 +/- 4%) appeared. The hindlimb vasodilation and MAP responses were unaffected by renal denervation. These results demonstrate that the baroreceptor afferents are an essential component of cardiovascular adjustments to VE, especially in the control of renal vascular conductance. They also suggest that renal vasodilation induced by VE is mediated by neural and hormonal mechanisms.
Asunto(s)
Volumen Sanguíneo/fisiología , Riñón/irrigación sanguínea , Riñón/inervación , Neuronas Aferentes/fisiología , Presorreceptores/fisiología , Anestesia , Animales , Aorta/inervación , Aorta/fisiología , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Masculino , Ratas , Ratas Wistar , Arteria Renal/inervación , Arteria Renal/fisiología , Circulación Renal/fisiología , Vagotomía , Vasodilatación/fisiologíaRESUMEN
Bilateral common carotid occlusion (BCO) over a period of 60 s in conscious rats produces a biphasic pressor response, consisting of an early (peak) and late (plateau) phase. In this study we investigated 1) the effects of lesions of the commissural nucleus of the solitary tract (commNTS) on the cardiovascular responses produced by BCO in conscious rats and 2) the autonomic and humoral mechanisms activated to produce the pressor response to BCO in sham- and commNTS-lesioned rats. Both the peak and plateau of the pressor response produced by BCO increased in commNTS-lesioned rats despite the impairment of chemoreflex responses induced by intravenous potassium cyanide. In sham rats sympathetic blockade with intravenous prazosin and metoprolol, but not vasopressin receptor blockade with the Manning compound, reduced both components of BCO. In commNTS-lesioned rats the sympathetic blockade or vasopressin receptor blockade reduced both components of BCO. The results showed 1) the sympathetic nervous system, but not vasopressin, is important for the pressor response to BCO during 60 s in conscious sham rats; 2) in commNTS-lesioned rats, despite chemoreflex impairment, BCO produces an increased pressor response dependent on sympathetic activity associated with vasopressin release; and 3) the increment in the pressor response to BCO in commNTS-lesioned rats seems to depend only on vasopressin secretion.
Asunto(s)
Presión Sanguínea/fisiología , Arterias Carótidas/fisiología , Vías Eferentes/fisiología , Núcleo Solitario/fisiología , Agonistas alfa-Adrenérgicos/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Antagonistas Adrenérgicos beta/farmacología , Animales , Arginina Vasopresina/farmacología , Presión Sanguínea/efectos de los fármacos , Células Quimiorreceptoras/efectos de los fármacos , Células Quimiorreceptoras/fisiología , Constricción , Electrólisis , Masculino , Metoprolol/farmacología , Fenilefrina/farmacología , Cianuro de Potasio/farmacología , Prazosina/farmacología , Presorreceptores/efectos de los fármacos , Presorreceptores/fisiología , Ratas , Ratas WistarRESUMEN
Both acute (1 day) lesions of the commissural nucleus of the solitary tract (commNTS) and aortic baroreceptor denervation increase pressor responses to bilateral common carotid occlusion (BCO) during a 60-second period in conscious rats. In this study, we investigated the following: (1) the effects of commNTS lesions on basal mean arterial pressure (MAP) and heart rate (HR) of aortic denervated (ADNx) rats; (2) the effects of acute commNTS lesions on pressor responses to BCO in ADNx rats; and (3) the effects of chronic (10 days) commNTS lesions on the pressor response to BCO. ADNx increased basal MAP and HR in sham-lesioned rats. Acute commNTS lesions abolished the MAP and HR increases observed in ADNx rats. Acute commNTS lesions increased the pressor responses to BCO in rats with intact-baroreceptor innervation but produced no additional change in the pressor response to BCO in ADNx rats. Chronic commNTS lesions did not change the pressor responses to BCO in rats with intact-baroreceptor innervation. The data show that acute commNTS lesions abolish the MAP increase produced by aortic baroreceptor denervation. They also suggest that acute commNTS lesions enhance the pressor response to BCO by partial withdrawal of aortic baroreceptor inputs into the NTS. Chronically, reorganization in the remaining aortic baroreceptor or in the baroreflex function as a whole might produce normalization of the cardiovascular responses to BCO.
Asunto(s)
Presión Sanguínea , Frecuencia Cardíaca , Presorreceptores/fisiopatología , Núcleo Solitario/fisiopatología , Animales , Aorta/inervación , Aorta/fisiopatología , Arterias Carótidas/patología , Arterias Carótidas/fisiopatología , Desnervación , Masculino , Ratas , Ratas WistarRESUMEN
The major aim of the present study was to evaluate the role of the rostral ventrolateral medulla (RVLM) in the maintenance of hypertension in rats subjected to long-term treatment with N(G)-nitro-L-arginine methyl ester (L-NAME) (70 mg/kg orally for 1 week). We inhibited or stimulated RVLM neurons with the use of drugs such as glycine, L-glutamate, or kynurenic acid in urethane-anesthetized rats (1.2 to 1.4 g/kg IV). Bilateral microinjection of glycine (50 nmol, 100 nL) into the RVLM of hypertensive rats produced a decrease in mean arterial blood pressure (MAP) from 158+/-4 to 71+/-4 mm Hg (P<0.05), which was similar to the decrease produced by intravenous administration of hexamethonium. In normotensive rats, glycine microinjection reduced MAP from 106+/-4 to 60+/-3 mm Hg (P<0.05). Glutamate microinjection into the RVLM produced a significant increase in MAP in both hypertensive rats (from 157+/-3 to 201+/-6 mm Hg) and normotensive rats (from 105+/-5 to 148+/-9 mm Hg). No change in MAP was observed in response to kynurenic acid microinjection into the RVLM in either group. These results suggest that hypertension in response to long-term L-NAME treatment is dependent on an increase in central sympathetic drive, mediated by RVLM neurons. However, glutamatergic synapses within RVLM are probably not involved in this response.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Hipertensión/fisiopatología , Bulbo Raquídeo/fisiopatología , NG-Nitroarginina Metil Éster/farmacología , Sistema Nervioso Simpático/fisiopatología , Animales , Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Glutámico/farmacología , Glicina/farmacología , Hipertensión/etiología , Ácido Quinurénico/farmacología , Masculino , Ratas , Ratas WistarRESUMEN
A well-known action of nitric oxide (NO) is to stimulate the soluble form of guanylyl cyclase, evoking an accumulation of cyclic GMP in target cells. The aim of the present study was to examine the effects of inhibition of guanylyl cyclase dependent on NO during cardiovascular responses induced by L-glutamate and S-nitrosoglutathione (SNOG) microinjected into the rostral ventrolateral medulla (RVLM) of awake rats. Three days before the experiments, adult male Wistar rats (280 to 320 g) were anesthetized for implantation of guide cannulas to the desired stereotaxic position (AP=-2.5 mm, L=1.8 mm) in relation to lambda. The cannulas were fixed to the skull with acrylic cement. Twenty-four hours before the experiments, a femoral artery and vein were cannulated for recording arterial pressure (AP) and heart rate (HR) and injection of anesthetic. Unilateral microinjections (100 nL) of L-glutamate (5 nmol/L) and SNOG (2.5 nmol/L) were made into the histologically confirmed RVLM. The cardiovascular responses to these drugs were evaluated before and after microinjection (3 nmol/L, 200 nL) of either methylene blue or oxodiazoloquinoxaline (ODQ). The hypertensive effect of L-glutamate was attenuated by 74% after methylene blue (DeltaAP=49+/-8 to 13+/-4 mm Hg) and by 80.5% after ODQ (DeltaAP=30+/-2 to 6+/-2 mm Hg). The increase in AP produced by SNOG was fully blocked by ODQ (DeltaAP=39+/-8 to 1+/-2 mm Hg). These data indicate that cyclic GMP mechanisms have a key role in glutamatergic neurotransmission in the RVLM of awake rats, and it is most probable that NO participates in this response.
Asunto(s)
Presión Sanguínea/fisiología , Ácido Glutámico/fisiología , Guanilato Ciclasa/fisiología , Bulbo Raquídeo/fisiología , Óxido Nítrico/fisiología , Transmisión Sináptica/fisiología , Animales , Presión Sanguínea/efectos de los fármacos , Ácido Glutámico/farmacología , Glutatión/análogos & derivados , Glutatión/farmacología , Masculino , Neuronas/fisiología , Donantes de Óxido Nítrico/farmacología , Compuestos Nitrosos/farmacología , Ratas , Ratas Wistar , S-NitrosoglutatiónRESUMEN
In this study we used a method that permits bilateral or unilateral microinjections of drugs into the rostral ventrolateral medulla (RVLM) of conscious, freely moving rats. There is only limited information about how sympathetic vasomotor tone is maintained by premotor RVLM neurons in conscious animals. It has long been known that glycine microinjection into the RVLM region leads to a decrease in blood pressure (BP) in anesthetized animals. In the present study we show that both unilateral and bilateral microinjection of glycine at the same dose used for anesthetized rats (50 nmol, 50 nL) into the RVLM increases BP in conscious animals. A similar response was also observed when the excitatory amino acid L-glutamate was microinjected into the RVLM. The microinjection of kynurenic acid into the RVLM did not change the basal level of BP but blocked the increase in BP after glycine or glutamate microinjection. A decrease in BP was only observed when low doses of glycine were used (1 to 10 nmol). We conclude that, in conscious animals, the hypertension occurring in response to high doses of glycine into the RVLM is dependent on glutamatergic synapses within the RVLM. A decrease in BP observed when low doses of glycine were used shows that in conscious animals, the RVLM, in association with other premotor neurons, is probably responsible for the maintenance of sympathetic vasomotor tone, because glycine is less effective in decreasing BP under these circumstances than in anesthetized animals.
Asunto(s)
Presión Sanguínea/fisiología , Ácido Glutámico/fisiología , Glicina/fisiología , Bulbo Raquídeo/fisiología , Sinapsis/fisiología , Animales , Neuronas/fisiología , Ratas , Ratas WistarRESUMEN
Several studies demonstrate that, within the ventral medullary surface (VMS), excitatory amino acids are necessary components of the neural circuits involved in the tonic and reflex control of respiration and circulation. In the present study we investigated the cardiorespiratory effects of unilateral microinjections of the broad spectrum glutamate antagonist kynurenic acid (2 nmol/200 nl) along the VMS of urethane-anesthetized rats. Within the VMS only one region was responsive to this drug. This area includes most of the intermediate respiratory area, partially overlapping the rostral ventrolateral medulla (IA/RVL). When microinjected into the IA/RVL, kynurenic acid produced a respiratory depression, without changes in mean arterial pressure or heart rate. The respiratory depression observed was characterized by a decrease in ventilation, tidal volume and mean inspiratory flow and an increase in respiratory frequency. Therefore, the observed respiratory depression was entirely due to a reduction in the inspiratory drive. Microinjections of vehicle (200 nl of saline) into this area produced no significant changes in breathing pattern, blood pressure or heart rate. Respiratory depression in response to the blockade of glutamatergic receptors inside the rostral VMS suggests that neurons at this site have an endogenous glutamatergic input controlling the respiratory cycle duration and the inspiratory drive transmission.
Asunto(s)
Animales , Masculino , Ratas , Antagonistas de Aminoácidos Excitadores/efectos adversos , Ácido Quinurénico/efectos adversos , Bulbo Raquídeo , Respiración/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Microinyecciones , Ratas WistarRESUMEN
Several studies demonstrate that, within the ventral medullary surface (VMS), excitatory amino acids are necessary components of the neural circuits involved in the tonic and reflex control of respiration and circulation. In the present study we investigated the cardiorespiratory effects of unilateral microinjections of the broad spectrum glutamate antagonist kynurenic acid (2 nmol/200 nl) along the VMS of urethane-anesthetized rats. Within the VMS only one region was responsive to this drug. This area includes most of the intermediate respiratory area, partially overlapping the rostral ventrolateral medulla (IA/RVL). When microinjected into the IA/RVL, kynurenic acid produced a respiratory depression, without changes in mean arterial pressure or heart rate. The respiratory depression observed was characterized by a decrease in ventilation, tidal volume and mean inspiratory flow and an increase in respiratory frequency. Therefore, the observed respiratory depression was entirely due to a reduction in the inspiratory drive. Microinjections of vehicle (200 nl of saline) into this area produced no significant changes in breathing pattern, blood pressure or heart rate. Respiratory depression in response to the blockade of glutamatergic receptors inside the rostral VMS suggests that neurons at this site have an endogenous glutamatergic input controlling the respiratory cycle duration and the inspiratory drive transmission.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/efectos adversos , Ácido Quinurénico/efectos adversos , Bulbo Raquídeo , Respiración/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Microinyecciones , Ratas , Ratas WistarRESUMEN
The aim of the present study was to examine the participation of NO in the rostral ventrolateral medulla (RVLM) of freely moving rats. We utilized NO donors and L-arginine, which were microinjected into the RVLM. Unilateral microinjection (100 nL) of 2.5 nmol sodium nitroprusside produced a biphasic response consisting of an initial, rapid increase in arterial pressure (AP) from 125+/-5 to 161+/-8 mm Hg (P<.01) and a second, long-lasting response with a progressive increase in AP (maximum delta peak, 34+/-9 mm Hg; P<.01). Another NO donor, S-nitroso-N-acetylpenicillamine (SNAP; 2.5 nmol), also produced immediate hypertension from 118+/-5 mm Hg to 168+/-7 mm Hg (P<.01) but without the second, long-lasting response. L-Arginine (5, 24, and 140 nmol) produced a gradual increase in AP. L-Glutamate (5 nmol) microinjected into the RVLM produced an increase in AP from 122+/-9 mm Hg to 171+/-8 mm Hg (P<.01) and bradycardia from 342+/-10 to 315+/-8 beats/min. This AP response was significantly attenuated, from 115+/-7 to 128+/-9 mm Hg (P<.05), after microinjection of methylene blue (3 nmol) without alterations in heart rate. These results indicate that NO may have an excitatory effect on the RVLM of freely moving rats, probably in association with glutamatergic synapses via cGMP mechanisms.
Asunto(s)
Bulbo Raquídeo/fisiología , Óxido Nítrico/fisiología , Animales , Arginina/farmacología , GMP Cíclico/fisiología , Ácido Glutámico/farmacología , Masculino , Bulbo Raquídeo/efectos de los fármacos , Microinyecciones , Penicilamina/análogos & derivados , Penicilamina/farmacología , Ratas , Ratas Wistar , S-Nitroso-N-AcetilpenicilaminaRESUMEN
We investigated the cardiorespiratory effects elicited by microinjections of L-glutamate (L-glu, 25 nmol, 200 nl) at various sites in the ventral medulla (VMS) of urethane-anesthetized rats. The results demonstrated that regions responsive to the drug are located along a column in the VMS extending from the VI cranial nerve to the first cervical nerve in the caudal medulla. Within this column three breathing patterns were elicited from four distinct areas. In the most rostral and caudal portion of this hypothetical column, the breathing patterns observed in response to L-glu were similar and characterized by increases in minute ventilation, tidal volume, inspiratory drive, respiratory frequency, mean arterial blood pressure (MAP) and heart rate (HR). In the regions located between the areas described above two different breathing patterns were obtained without significant changes in MAP or HR. These patterns were characterized by decreases and increases in the respiratory indices analyzed, with the exception of respiratory frequency, which decreased in both regions. These results suggest that within the VMS discrete areas may act as functional units modulating cardiorespiratory responses while in others these functions are spatially segregated.
Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Ácido Glutámico/farmacología , Bulbo Raquídeo/efectos de los fármacos , Respiración/efectos de los fármacos , Animales , Fenómenos Fisiológicos Cardiovasculares , Masculino , Bulbo Raquídeo/anatomía & histología , Bulbo Raquídeo/fisiología , Microinyecciones , Ratas , Ratas Wistar , Respiración/fisiología , Fenómenos Fisiológicos Respiratorios , Sistema Respiratorio/efectos de los fármacosRESUMEN
In this study we determined the cardiovascular effects produced by microinjection of angiotensin peptides [Angiotensin-(1-7) and Angiotensin II] and angiotensin antagonists (losartan, L-158,809, CGP 42112A. Sar1-Thr8-Ang II, A-779) into the rostral ventrolateral medulla of freely moving rats. Microinjection of angiotensins (12.5-50 pmol) produced pressor responses associated to variable changes in heart rate, usually tachycardia. Unexpectedly, microinjection of both AT1 and AT2 ligands produced pressor effects at doses that did not change blood pressure in anesthetized rats. Conversely, microinjection of Sar1-Thr8-Ang II and the selective Ang-(1-7) antagonist, A-779, produced a small but significant decrease in MAP an HR. These findings suggest that angiotensins can influence the tonic activity of vasomotor neurons at the RVLM. As previously observed in anesthetized rats, our results further suggest a role for endogenous Ang-(1-7) at the RVLM. The pressor activity of the ligands for AT1 and AT2 angiotensin receptor subtypes at the RVLM, remains to be clarified.
Asunto(s)
Angiotensina II/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Bulbo Raquídeo/fisiología , Fragmentos de Péptidos/farmacología , Angiotensina I , Angiotensina II/administración & dosificación , Angiotensina II/análogos & derivados , Antagonistas de Receptores de Angiotensina , Animales , Compuestos de Bifenilo/administración & dosificación , Compuestos de Bifenilo/farmacología , Imidazoles/administración & dosificación , Imidazoles/farmacología , Losartán , Masculino , Bulbo Raquídeo/efectos de los fármacos , Microinyecciones , Oligopéptidos/administración & dosificación , Oligopéptidos/farmacología , Fragmentos de Péptidos/administración & dosificación , Ratas , Ratas Wistar , Tetrazoles/administración & dosificación , Tetrazoles/farmacología , Factores de TiempoRESUMEN
The aim of the present study was to examine the participation of the rostral ventrolateral medulla (RVLM) in the maintenance of hypertension in rats submitted to the renovascular Goldblatt (two-kidney, one clip) procedure. We inhibited or stimulated this area with the use of drugs such as glycine, L-glutamate, or kynurenic acid. (1) Bilateral microinjection of glycine (100 nmol, 200 nL, n = 13) into the RVLM of hypertensive rats produced a decrease in mean arterial blood pressure (MAP) from 177.2 +/- 29.3 to 102.3 +/- 20.9 mm Hg (P < .05), which was similar to the decrease produced by intravenous administration of hexamethonium. The inhibition of RVLM with glycine in normotensive rats produced a decrease in MAP from 106 +/- 17.1 to 59.7 +/- 7.3 mm Hg (P < .05, n = 9). (2) An impressive increase in MAP from 153.3 +/- 16.3 to 228 +/- 34.9 mm Hg (P < .05) occurred in hypertensive rats after microinjection of L-glutamate (50 nmol, 200 nL, n = 6) into the RVLM. The same procedure caused a significant but less intense increase in MAP from 105 +/- 13.8 to 148.3 +/- 24.9 mm Hg in normotensive rats (P < .05, n = 6). (3) A decrease in MAP from 151.6 +/- 25.3 to 96.8 +/- 22.5 mm Hg occurred in hypertensive rats after microinjection of the broad-spectrum glutamate antagonist kynurenic acid (4 nmol, 200 nL, n = 6) into the RVLM, whereas the same procedure did not change MAP in normotensive animals (n = 6). Heart rate was not significantly affected in any group.(ABSTRACT TRUNCATED AT 250 WORDS)