Brainstem areas activated by intermittent apnea in awake unrestrained rats.

We investigated the role of the autonomic nervous system to cardiovascular responses to obstructive apnea in awake, unrestrained rats, and measured expression of Fos induced by apnea in the brainstem. We implanted a tracheal balloon contained in a rigid tube to allow the induction of apnea without inducing pain in the trachea. During bouts of 15s of apnea, heart rate fell from 371±8 to 161±11bpm (mean±SEM, n=15, p<0.01) and arterial pressure increased from 115±2 to 131±4mmHg (p<0.01). Bradycardia was due to parasympathetic activity because it was blocked by the muscarinic antagonist, methylatropine. The pressor response was due to vasoconstriction caused by sympathetic activation because it was blocked by the α1 antagonist, prazosin. Apnea induced Fos expression in several brainstem areas involved in cardiorespiratory control such as the nucleus of the solitary tract (NTS), ventrolateral medulla (VLM), and pons. Ligation of the carotid body artery reduced apnea-induced bradycardia, blocked heart rate responses to i.v. injection of cyanide, reduced Fos expression in the caudal NTS, and increased Fos expression in the rostral VLM. In conclusion, apnea activates neurons in regions that process signals from baroreceptors, chemoreceptors, pulmonary receptors, and regions responsible for autonomic and respiratory activity both in the presence and absence of carotid chemoreceptors.

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume.

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.

Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume

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.

Avaliação da aptidão cardiorrespiratória de crianças com displasia broncopulmonar / Cardiorespiratory capacity assessment on children with bronchopulmonary dysplasia

OBJETIVO: Avaliar a aptidão cardiorrespiratória e verificar a presença de broncoespasmo induzido pelo exercício (BIE) em crianças com displasia broncopulmonar (DBP). MÉTODO: Foram realizadas prova de função pulmonar e análise de gases em um teste cardiopulmonar, em 46 crianças com idade entre 7 a 10 anos, formando três grupos: crianças nascidas pré-termo com DBP, (DBP, n= 13); crianças nascidas pré-termo sem DBP, (RNPT, n= 13); e crianças saudáveis nascidas a termo, (Controle, n= 20). RESULTADOS: A duração dos testes foi 7,70 ± 1,49; 9,1 ± 2,02 e 8,4 ± 2,12 min; o VO2máximo foi 35,98 ± 5,33; 38,99 ± 6,73 e 34,91 ± 6,09 ml/kg/min; e a VE foi 28,54 ± 7,39; 28,84 ± 5,98 e 28,96 ± 6,96 l/min para os grupos DBP, RNPT e Controle, respectivamente. Não foram encontradas diferenças significantes entre os grupos (p> 0,05). A FCmáxima foi 188 ± 9,37; 196 ± 5,15 e 197 ± 10,90 bpm; a taxa de troca gasosa máxima (R) foi 1,21 ± 0,22; 1,10 ± 0,06 e 1,05 ± 0,05 para os grupos DBP, RNPT e Controle, respectivamente, sendo esses valores diferentes entre o grupo Controle e DBP (p< 0,05). Os valores do VEF1 pré e VEF1 pós-exercício foram de 99 ± 12 por cento e 94 ± 14 por cento; 100 ± 14 por cento e 100 ± 15 por cento; e 102 ± 15 por cento e 101 ± 15 por cento, para os grupos DBP, RNPT e Controle, respectivamente. Na comparação do VEF1 pré e pós-exercício não houve diferenças significantes e nem caracterização de BIE nos grupos. CONCLUSÃO: A diferença encontrada no R pode ser relacionada a alterações ventilatórias e à difusão pulmonar. A aptidão cardiorrespiratória das crianças com DBP é semelhante à dos grupos RNPT e Controle.

OBJECTIVE: To assess cardiorespiratory capacity and investigate the presence of exercise-induced bronchospasm among children with bronchopulmonary dysplasia. METHOD: Pulmonary function tests and gas analyses were performed in a cardiopulmonary test on 46 children aged 7-10 years. Three groups were formed: children born prematurely with bronchopulmonary dysplasia (BPD; n= 13), children born prematurely without bronchopulmonary dysplasia (Preterm; n= 13) and healthy children born at full term (Control; n= 20). RESULTS: The test duration was 7.70 ± 1.49; 9.1 ± 2.02 and 8.4 ± 2.12 min; VO2max was 35.98 ± 5.33; 38.99 ± 6.73 and 34.91 ± 6.09 ml/kg/min; and VE was 28.54 ± 7.39; 28.84 ± 5.98 and 28.96 ± 6.96 l/min for the BPD, Preterm and Control groups respectively. There were no significant differences between the groups (p> 0.05). The maximum heart rate was 188 ± 9.37; 196 ± 5.15 and 197 ± 10.90 beats/min and the respiratory exchange ratio (RER) was 1.21 ± 0.22; 1.10 ± 0.06 and 1.05 ± 0.05, for the BPD, Preterm and Control groups respectively, and there was a significant difference between the BPD and Control groups (p< 0.05). The FEV1 values before and after exercise were 99 ± 12 percent and 94 ± 14 percent; 100 ± 14 percent and 100 ± 15 percent; and 102 ± 15 percent and 101 ± 15 percent, for the BPD, Preterm and Control groups respectively. Comparison of FEV1 before and after exercise did not show any significant differences and exercise-induced bronchospasm was not characterized, in any of the groups. CONCLUSION: The difference in RER may be related to abnormal ventilation and pulmonary diffusion. The cardiorespiratory capacity of children with BPD was similar to that of the Preterm and Control groups.

Performance of two-dimensional Doppler echocardiography for the assessment of infarct size and left ventricular function in rats.

Although echocardiography has been used in rats, few studies have determined its efficacy for estimating myocardial infarct size. Our objective was to estimate the myocardial infarct size, and to evaluate anatomic and functional variables of the left ventricle. Myocardial infarction was produced in 43 female Wistar rats by ligature of the left coronary artery. Echocardiography was performed 5 weeks later to measure left ventricular diameter and transverse area (mean of 3 transverse planes), infarct size (percentage of the arc with infarct on 3 transverse planes), systolic function by the change in fractional area, and diastolic function by mitral inflow parameters. The histologic measurement of myocardial infarction size was similar to the echocardiographic method. Myocardial infarct size ranged from 4.8 to 66.6% when determined by histology and from 5 to 69.8% when determined by echocardiography, with good correlation (r = 0.88; P < 0.05; Pearson correlation coefficient). Left ventricular diameter and mean diastolic transverse area correlated with myocardial infarct size by histology (r = 0.57 and r = 0.78; P < 0.0005). The fractional area change ranged from 28.5 +/- 5.6 (large-size myocardial infarction) to 53.1 +/- 1.5% (control) and correlated with myocardial infarct size by echocardiography (r = -0.87; P < 0.00001) and histology (r = -0.78; P < 00001). The E/A wave ratio of mitral inflow velocity for animals with large-size myocardial infarction (5.6 +/- 2.7) was significantly higher than for all others (control: 1.9 +/- 0.1; small-size myocardial infarction: 1.9 +/- 0.4; moderate-size myocardial infarction: 2.8 +/- 2.3). There was good agreement between echocardiographic and histologic estimates of myocardial infarct size in rats.

Performance of two-dimensional Doppler echocardiography for the assessment of infarct size and left ventricular function in rats

Although echocardiography has been used in rats, few studies have determined its efficacy for estimating myocardial infarct size. Our objective was to estimate the myocardial infarct size, and to evaluate anatomic and functional variables of the left ventricle. Myocardial infarction was produced in 43 female Wistar rats by ligature of the left coronary artery. Echocardiography was performed 5 weeks later to measure left ventricular diameter and transverse area (mean of 3 transverse planes), infarct size (percentage of the arc with infarct on 3 transverse planes), systolic function by the change in fractional area, and diastolic function by mitral inflow parameters. The histologic measurement of myocardial infarction size was similar to the echocardiographic method. Myocardial infarct size ranged from 4.8 to 66.6 percent when determined by histology and from 5 to 69.8 percent when determined by echocardiography, with good correlation (r = 0.88; P < 0.05; Pearson correlation coefficient). Left ventricular diameter and mean diastolic transverse area correlated with myocardial infarct size by histology (r = 0.57 and r = 0.78; P < 0.0005). The fractional area change ranged from 28.5 ± 5.6 (large-size myocardial infarction) to 53.1 ± 1.5 percent (control) and correlated with myocardial infarct size by echocardiography (r = -0.87; P < 0.00001) and histology (r = -0.78; P < 00001). The E/A wave ratio of mitral inflow velocity for animals with large-size myocardial infarction (5.6 ± 2.7) was significantly higher than for all others (control: 1.9 ± 0.1; small-size myocardial infarction: 1.9 ± 0.4; moderate-size myocardial infarction: 2.8 ± 2.3). There was good agreement between echocardiographic and histologic estimates of myocardial infarct size in rats.

Teste de caminhada de seis minutos em adultos eutroficos e obesos / The six minute walk test in normal and obese adults

O teste de caminhada frequentemente e utilizado para demonstrar os efeitos das doencas cardiovasculares e respiratorias sobre a capacidade fisica, como tambem para tederminar os efeitos de tratamentos aplicados. Participaram do estudo 46 pessoas, divididas em 5 grupos por faixa de IMC. O grupo 1 foi constituido por 18 pesoas com IMC de 20 a 24,9 Kg/m o grupo 2, por 12 pessoas com IMC de 25 a 29,9 Kg/m, o grupo 3, por 6 pessoas com IMC de 30 a 34,9 Kg/m o grupo 4, por 1 pessoas com IMC de 35 a 39,9 Kg/m e o grupo 5, por 9 pessoas com IMC > 40 kg/m. Os voluntarios realizaram um total de quatro testes de caminhada, de forma padronizada com acompanhamento do avaliador durante a caminhada. Os resultados mostraram que no 4§ teste a distancia percorrida foi maior que no 1§ teste (p< 0,01) no intervalo de tempo de 0 a 2 minutos, a distancia caminhada foi maior que nos demais intervalos de tempo (p< 0,01) com o auento do peso corporal houve diminuicao da distancia caminhada (p < 0,01), em media, distancia caminhada de 760m +50,6m (grupo 1), 731 m +71,9m (grupo 2), 680 m +56,7 m (grupo 3), 663 m (grupo 4) e 596 m + 61,8 m (grupo 5). O porcentual de gordura foi a medida antropometrica que melhor se correlacionou com distancia caminhada (r= -0,85 e p < 0,05), seguindo pelo de massa corporal (r = -0, 65) e pela relacao cintura/quadril (r= -0,56),somente para o sexo masculino. Concluiu-se que o aumento do peso corporal interfere na capacida fisica, diminuindo a distancia caminhada. no intervalo de tempo de 0 a 2 minutos, ocorre o melhor desempenho fisico. o efeito aprendizado influencia a distancia percorrida. e o porcentual de gordura e a medida antropometrica que melhor se correlaciona com distancia percorrida

Role of the medulla oblongata in hypertension.

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.

Glutamatergic and GABAergic inputs to the RVL mediate cardiovascular adjustments to noxious stimulation.

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.

Afferent pathways in cardiovascular adjustments induced by volume expansion in anesthetized rats.

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.

Effects of acute AV3V lesions on renal and hindlimb vasodilation induced by volume expansion.

The role of the anteroventral third ventricle (AV3V) region in the cardiovascular adjustments to volume expansion (VE) with 4% Ficoll (1% body weight, 1.4 mL/min) was studied in urethane-anesthetized rats. In sham-lesioned animals, VE produced a transitory (

Respiratory effects of kynurenic acid microinjected into the ventromedullary surface of the rat

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.

Respiratory effects of kynurenic acid microinjected into the ventromedullary surface of the rat.

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.

Cardiorespiratory effects of L-glutamate microinjected into the rat ventral medulla.

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.

Monosynaptic projections from the nucleus tractus solitarii to C1 adrenergic neurons in the rostral ventrolateral medulla: comparison with input from the caudal ventrolateral medulla.

The rostral ventrolateral medulla (RVL) contains reticulospinal adrenergic (C1) neurons that are thought to be sympathoexcitatory and that form the medullary efferent limb of the baroreceptor reflex pathway. The RVL receives direct projections from two important autonomic regions, the caudal ventrolateral medulla (CVL) and the nucleus tractus solitarii with immunocytochemical identification of C1 adrenergic neurons in the RVL to compare the morphology of afferent input from these two autonomic regions into the RVL. NTS (n = 203) and CVL (n = 380) efferent terminals had similar morphology and vesicular content, but CVL efferent terminals were slightly larger than NTS efferent terminals. Overall, efferent terminals from either region were equally likely to contact adrenergic neurons in the RVL (21% for NTS, 25% for CVL). Although efferents from both regions formed both symmetric and asymmetric synapses, NTS efferent terminals were statistically more likely to form asymmetric synapses than CVL efferent terminals. CVL efferent terminals were more likely to contact adrenergic somata than were NTS efferents, which usually contacted dendrites. These findings 1) support the hypothesis that a portion of NTS efferents to the RVL may be involved in sympathoexcitatory, e.g., chemoreceptor, reflexes (via asymmetric synapses), whereas those from the CVL mediate sympathoinhibition (via symmetric synapses); and 2) provide an anatomical substrate for differential postsynaptic modulation of C1 neurons by projections from the NTS and CVL. With their more frequent somatic localization, CVL inhibitory inputs may be more influential than excitatory NTS inputs in determining the discharge of RVL neurons.

Evidence for neuronal release of isotopically labelled glycine from the rat ventral medullary surface in vivo.

Spontaneous and stimulus-induced release of isotopically labelled glycine was studied in the superfused rat dorsal or ventral medullary surface in vivo. Superfusion of the ventral medullary surface of anesthetized (urethane, 1.2 g/kg, ip) male adult Wistar rats (250-350 g) with high K+ (40 mM) surrogate cerebrospinal fluid (CSF) produced an average increase of 45% over the spontaneous efflux of exogeneously applied glycine (N = 5, P < 0.01). In experiments in which the calcium of the CSF was replaced by an equimolar amount of magnesium, the increase in glycine efflux in response to high K+ was reduced to 15%, a value not statistically different from that observed in control experiments (N = 6). Veratridine stimulation evoked a large (80%) increase in glycine efflux (N = 5, P < 0.001), which was inhibited by tetrodotoxin. High potassium or veratridine failed to modify spontaneous release of glycine on the dorsal medullary surface. Results obtained in control experiments showed that neither high K+ nor veratridine is effective in modifying spontaneous efflux of [3H]-leucine or [3H]-inulin on the ventral or dorsal medullary surface. These data support the hypothesis that glycine is a neurotransmitter on the ventral medullary surface and that it may be part of neural pathways involved in cardiorespiratory regulation present in this region.

Evidence for neuronal release of isotopically labelled glycine from the rat ventral medullary surface in vivo

Spontaneous and stimulus-induced release of isotopically labelled glycine was studied in the superfused rat dorsal or ventral medullary surface in vivo. Superfusion of the ventral medullary surface of anesthetized (urethane, 1.2 g/kg, ip) male adult Wistar rats (250-350 g) with high K+ (40 mM) surrogate cerebrospinal fluid (CSF) produced an average increase of 45 per cent over the spontaneous efflux of exogenously applied glycine (N = 5, P<0.01). In experiments in which the calcium of the CSF was replaced by an equimolar amount of magnesium, the increase in glycine efflux in response to high K+ was reduced to 15 per cent, a value not statistically different from that observed in control experiments (N = 6). Veratridine stimulation evoked a large (80 per cent) increase in glycine efflux (N = 5, P<0.001), which was inhibited by tetrodotoxin. High potassium or veratridine failed to modify spontaneous release of glycine on the dorsal medullary surface. Results obtained in control experiments showed that neither high K+ nor veratridine is effective in modifying spontaneous efflux of [(3)H]-leucine or [(3)H]-inulin on the ventral or dorsal medullary surface. These data support the hypothesis that glycine is a neurotransmitter on the ventral medullary surface and that it may be part of neural pathways involved in cardiorespiratory regulation present in this region.

Cardiovascular adjustments in limb retraction provoked by noxious stimulation in decerebrate and spinal cats. Evidence for a somatotopic organization.

Arterial blood pressure, heart rate and iliac blood flow were continuously recorded in 61 adult cats and their alteration induced by noxious stimulation of the interdigital spaces of the four limbs was studied in intact (anesthetized) and in decerebrate and spinal preparations. Noxious stimulation of any limb in the decerebrate animals provoked retraction 61% of the times and an increase of blood pressure and heart rate in approximately 80% of the stimulations. Stimulation of a hindlimb provoked an increase of blood flow in the same limb in about 80% of the stimulations, due to active vasodilation. Contralateral stimulation provoked a smaller increase of blood flow but with an increase in vascular resistance, indicating some degree of vasoconstriction. Stimulation of the forelimbs induced small increases of blood flow in the hindlimbs but the calculated vascular resistance was higher than the basal values, also indicating vasoconstriction. Neuromuscular blockade with gallamine did not affect the increase of hindlimb blood flow, suggesting a central regulation of the intricate distribution of blood to the limbs. The vasodilation was not due to activation of sympathetic cholinergic vasodilator neurons inasmuch as the blood flow responses were not affected by cholinergic blockade with atropine. In spinal animals, stimulation of any limb provoked small increases of blood pressure, extremely low degrees of tachycardia and an increase of hindlimb blood flow, with active vasodilation. Neuromuscular paralysis, however, abolished the adjustments of blood flow in the hindlimbs, indicating that metabolites and/or sensory information caused by muscle contraction induced them. In intact cats anesthetized with sodium pentobarbiturate, blood pressure and heart rate increased under noxious stimulation, although less than in the decerebrate animals. Nearly 40% of the stimulations provoked hypotension rather than hypertension. Blood flow increased due to stimulation of any limb but, as in the decerebrate preparation, there was active vasodilation in the ipsilateral hindlimb and vasoconstriction in the contralateral one.

Cardiovascular adjustments in limb retraction provoked by noxious stimulation in decerebrate and spinal cats: evidence for a somatotopic organization

Arterial blood pressure, heart rate and iliac blood flow were continuously recorded in 61 adult cats and their alteration induced by noxious stimulation of the interdigital spaces of the four limbs was studied in intact (anesthetized) and in decerebrate and spinal preparations. Noxious stimulation of any limb in the decerebrate animals provoked retraction 61 percent of the times and an increase of blood pressure and heart rate in approximately 80 percent of the stimulations. Stimulations of a hindlimb provoked an increase of blood flow in the same limb in about 80 percent of the stimulations, due to active vasodilation. Contralateral stimulation provoked as smaller increase of blood flow but with an increase in vascular resistance, indicating some degree of vasoconstriction. Stimulation of the forelimbs induced small increases of blood flow in the hindlimbs but the calculated vascular resistance was higher than the basal values, also indicating vasoconstriction. Neuromuscular blockade with gallamine did not affect the increase of hindlimb blood flow, suggesting a central regulation of the intricate distribution of blood to the limbs...

A fall in arterial blood pressure produced by inhibition of the caudalmost ventrolateral medulla: the caudal pressor area.

The caudal edge of the ventrolateral medulla was mapped to localize sites where microinjections of L-glutamate (L-glu) produce pressor responses in paralyzed and artificially ventilated urethane-anesthetized rats. Pressor responses ranging from 15 to 65 mmHg were obtained when L-Glu (0.25 M, 200 nl) was microinjected in the ventral medullary surface within an area localized between the rootlets of the XII and first cervical nerves, lateral to the pyramids and just medial to the spinal roots of the XI cranial nerve. This area has been called the caudal pressor area (CPA). Inhibition of the CPA by microinjection of GABA or glycine resulted in marked falls (15-45 mmHg) of arterial blood pressure (AP). Hypotension in response to CPA inhibition was also obtained in unanesthetized decerebrate animals. Cardiovascular responses to CPA stimulation or inhibition depend on the activity of neurons in the rostral ventrolateral medulla (RVLM). During hypotension provoked by RVLM inhibition, pressor responses to CPA stimulation were abolished. Conversely, pressor responses to RVLM stimulation were maintained during hypotension produced by inhibition of CPA. Pressor response to bilateral carotid occlusion were not reduced by CPA inhibition. We conclude that cells in the caudal most ventrolateral medulla exert a tonic pressor activity that contributes to maintenance of basal levels of the vasomotor tone and arterial blood pressure, its inhibition, however, does not prevent the pressor response to carotid occlusion.