Commissural NTS lesions enhance the pressor response to central cholinergic and adrenergic activation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Enhanced pressor response to carotid occlusion in commNTS-lesioned rats: possible efferent mechanisms

Bilateral common carotid occlusion (BCO) over a period of 60 s in conscious rats produces a biphasic presser 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 presser response to BCO in sham- and commNTS-lesioned rats. Both the peak and plateau of the presser 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 presser response to BCO during 60 s in conscious sham rats; 2) in commNTS-lesioned rats, despite chemoreflex impairment, BCO produces an increased presser response dependent on sympathetic activity associated with vasopressin release; and 3) the increment in the presser response to BCO in commNTS-lesioned rats seems to depend only on vasopressin secretion.

Control of breathing and blood pressure by parafacial neurons in conscious rats

New Findings: • What is the central question of this study? The main purpose of the present manuscript was to investigate the cardiorespiratory responses to hypoxia or hypercapnia in conscious rats submitted to neuronal blockade of the parafacial region. We clearly showed that the integrity of parafacial region is important for the respiratory responses elicited by peripheral and central chemoreflex activation in freely behavior rats. • What is the main finding and its importance? Since the parafacial region is part of the respiratory rhythm generator, they are essential for postnatal survival, which is probably due to their contribution to chemoreception in conscious rats. The retrotrapezoid nucleus (RTN), located in the parafacial region, contains glutamatergic neurons that express the transcriptor factor Phox2b and that are suggested to be central respiratory chemoreceptors. Studies in anaesthetized animals or in vitro have suggested that RTN neurons are important in the control of breathing by influencing respiratory rate, inspiratory amplitude and active expiration. However, the contribution of these neurons to cardiorespiratory control in conscious rats is not clear. Male Holtzman rats (280-300 g, n= 6-8) with bilateral stainless-steel cannulae implanted into the RTN were used. In conscious rats, the microinjection of the ionotropic glutamatergic agonist NMDA (5 pmol in 50 nl) into the RTN increased respiratory frequency (by 42%), tidal volume (by 21%), ventilation (by 68%), peak expiratory flow (by 24%) and mean arterial pressure (MAP, increased by 16 ± 4, versus saline, 3 ± 2 mmHg). Bilateral inhibition of the RTN neurons with the GABAA agonist muscimol (100 pmol in 50 nl) reduced resting ventilation (52 ± 34, versus saline, 250 ± 56 ml min-1 kg-1 with absolute values) and attenuated the respiratory response to hypercapnia and hypoxia. Muscimol injected into the RTN slightly reduced resting MAP (decreased by 13 ± 7, versus saline, increased by 3 ± 2 mmHg), without changing the effects of hypercapnia or hypoxia on MAP and heart rate. The results suggest that RTN neurons activate facilitatory mechanisms important to the control of ventilation in resting, hypoxic or hypercapnic conditions in conscious rats. © 2012 The Authors. Experimental Physiology © 2012 The Physiological Society.

Differential modulation of sympathetic and respiratory activities by cholinergic mechanisms in the nucleus of the solitary tract in rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Leptin into the ventrolateral medulla facilitates chemorespiratory response in leptin-deficient (ob/ob) mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Participation of the dorsal periaqueductal grey matter in the hypoxic ventilatory response in unanaesthetized rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Respiratory manifestations of panic disorder in animals and humans: A unique opportunity to understand how supramedullary structures regulate breathing

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The nucleus of the solitary tract and the coordination of respiratory and sympathetic activities

It is well known that breathing introduces rhythmical oscillations in the heart rate and arterial pressure levels. Sympathetic oscillations coupled to the respiratory activity have been suggested as an important homeostatic mechanism optimizing tissue perfusion and blood gas uptake/delivery. This respiratory-sympathetic coupling is strengthened in conditions of blood gas challenges (hypoxia and hypercapnia) as a result of the synchronized activation of brainstem respiratory and sympathetic neurons, culminating with the emergence of entrained cardiovascular and respiratory reflex responses. Studies have proposed that the ventrolateral region of the medulla oblongata is a major site of synaptic interaction between respiratory and sympathetic neurons. However, other brainstem regions also play a relevant role in the patterning of respiratory and sympathetic motor outputs. Recent findings suggest that the neurons of the nucleus of the solitary tract (NTS), in the dorsal medulla, are essential for the processing and coordination of respiratory and sympathetic responses to hypoxia. The NTS is the first synaptic station of the cardiorespiratory afferent inputs, including peripheral chemoreceptors, baroreceptors and pulmonary stretch receptors. The synaptic profile of the NTS neurons receiving the excitatory drive from afferent inputs is complex and involves distinct neurotransmitters, including glutamate, ATP and acetylcholine. In the present review we discuss the role of the NTS circuitry in coordinating sympathetic and respiratory reflex responses. We also analyze the neuroplasticity of NTS neurons and their contribution for the development of cardiorespiratory dysfunctions, as observed in neurogenic hypertension, obstructive sleep apnea and metabolic disorders.

Control of respiratory and cardiovascular functions by leptin

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Facilitation of breathing by leptin effects in the central nervous system

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hypoxic and hypercapnic ventilatory responses in rats with polycystic ovaries

In female rats, a single injection of estradiol valerate (EV) results in effects that are similar to those observed in women with polycystic ovary syndrome (PCOS). We hypothesized that EV-induced PCOS affects breathing control based on evidence showing an influence of sex hormones on ventilation. To test this hypothesis, we studied the effects of EV treatment on the ventilation of female rats in air, in 7% CO2 and in 7% O2, at 30, 45 and 60 days after EV injection. The group examined 30 days after EV treatment showed a 61% reduction in the hypercapnic ventilatory response compared to the control group. Basal ventilation, hypoxic ventilatory response, and body temperature were not affected. These results, suggest that the hormonal changes observed in PCOS may result in a temporary inhibition of the central chemoreflex but do not influence basal ventilation or the hypoxic peripheral chemoreflex.

Coupling between respiratory and sympathetic activities as a novel mechanism underpinning neurogenic hypertension

Enhanced sympathetic outflow to the heart and resistance vessels greatly contributes to the onset and maintenance of neurogenic hypertension. There is a consensus that the development of hypertension (clinical and experimental) is associated with an impairment of sympathetic reflex control by arterial baroreceptors. More recently, chronic peripheral chemoreflex activation, as observed in obstructive sleep apnea, has been proposed as another important risk factor for hypertension. In this review, we present and discuss recent experimental evidence showing that changes in the respiratory pattern, elicited by chronic intermittent hypoxia, play a key role in increasing sympathetic activity and arterial pressure in rats. This concept parallels results observed in other models of neurogenic hypertension, such as spontaneously hypertensive rats and rats with angiotensin II–salt-induced hypertension, pointing out alterations in the central coupling of respiratory and sympathetic activities as a novel mechanism underlying the development of neurogenic hypertension.

Glial cells modulate the synaptic transmission of NTS neurons sending projections to ventral medulla of Wistar rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acute exercise adjustments of cardiovascular autonomic control in diabetic rats

Introduction: We evaluated the role of cardiovascular autonomic changes in hemodynamics at rest and in response to exercise in streptozotocin-induced diabetic rats. Methods: Male Wistar rats were divided into nondiabetic (ND, n = 8) and diabetic (D, n = 8) groups. Arterial pressure signals were recorded in the basal state and after atropine or propranolol injections at rest, during exercise and during recovery. Results: At rest, vagal tonus was reduced in D (37 +/- 3 bpm) in comparison with the ND group (61 +/- 9 bpm). Heart rate during exercise was lower in D in relation to ND rats associated with reduced vagal withdrawal in the D group. The D rats had an increase in vagal tonus in the recovery period (49 +/- 6 bpm). Conclusions: Exercise-induced hemodynamic adjustment impairment in diabetic rats was associated with reduced cardiac vagal control. The vagal dysfunction was attenuated after aerobic exercise, reinforcing the positive role of this approach in the management of cardiovascular risk in diabetics. Muscle Nerve 46: 96101, 2012

Dynamic Aerobic Exercise Induces Baroreflex Improvement in Diabetic Rats

The objective of the present study was to investigate the effects of an acute aerobic exercise on arterial pressure (AP), heart rate (HR), and baroreflex sensitivity (BRS) in STZ-induced diabetic rats. Male Wistar rats were divided into control (n = 8) and diabetic (n = 8) groups. AP, HR, and BRS, which were measured by tachycardic and bradycardic (BR) responses to AP changes, were evaluated at rest (R) and postexercise session (PE) on a treadmill. At rest, STZ diabetes induced AP and HR reductions, associated with BR impairment. Attenuation in resting diabetes-induced AP (R: 103 +/- 2 versus PE: 111 +/- 3 mmHg) and HR (R: 290 +/- 7 versus PE:328 +/- 10 bpm) reductions and BR dysfunction (R: -0.70 +/- 0.06 versus PE:-1.21 +/- 0.09 bpm/mmHg) was observed in the postexercise period. In conclusion, the hemodynamic and arterial baro-mediated control of circulation improvement in the postexercise period reinforces the role of exercise in the management of cardiovascular risk in diabetes.