Utilizando Análise Espectral (FFT) para quantificar a variabilidade autonômica no animal intacto, analisamos pressão arterial, intervalo de pulso (IP) e fluxo sangüíneo no repouso e no exercício, em ratos normotensos (WKY) e hipertensos (SHR), sedentários (S) ou treinados (T), após pré-tratamento do NTS/DMV com veículo e antagonista de ocitocina (OTant). As principais alterações foram relacionadas à freqüência cardíaca (FC) e ao IP: bradicardia de repouso em WKYT e SHRT; aumento na resposta taquicárdica do exercício após OTant apenas nos WKYT. No repouso, os SHR apresentaram queda da variância do IP com diminuição dos componentes de baixa (LF-simpático) e alta (HF-vago) freqüências, corrigidas pelo T. No exercício houve queda dos componentes espetrais do IP nos grupos experimentais, exceto o HF que não diminuiu nos WKYT. OTant no NTS/DMV reduziu o HF dos SHRT no repouso e exercício; a ausência da queda do HF nos WKYT foi abolida. Resultados indicam a importância da ocitocina agindo sobre o vago na modulação da FC basal e da taquicardia do exercício apenas em T. / Using Spectral Analysis (FFT) to quantify the autonomic variability in intact animal, we analyzed blood pressure, pulse interval (PI) and blood flow at rest and during exercise, in normotensive (WKY) and hypertensive (SHR) rats, sedentary (S) or trained (T), after solitary vagal complex (NTS/DMV) pre-treatment with vehicle and oxytocin antagonist (OTant). The main changes were related to heart rate (HR) and PI: rest bradycardia in WKYT and SHRT; increased exercise tachycardia after OTant only in WKYT. At rest, SHR presented a fall of in PI variance with decreased low (LF-simpathetic) and high (HF-vagal) frequencies components that were normalized by T. During exercise, the spectral components decreased in the experimental groups, except HF unchanged in WKYT. OTant into the NTS/DMV reduced the HF of the SHRT at rest and exercise; the absence of the fall in HF of WKYT was abolished. Results indicate the importance of oxytocin acting on vagus in the modulation of basal HR and exercise tachycardia only in T rats.

Heart rate variability (HRV) reflects dynamic variation in sympathetic and parasympathetic nervous system (SNS and PNS) activity. The parasympathetic vagus nerve is responsible for HRV between 0.12 and 0.4 Hz, which is thought to index the capacity for effective coping, and is linked to physical and emotional well-being. Yogic breathing to increase vagal activity is often paced below 0.12 Hz (< 7.2 breaths per minute (BrPM)), where its impact HRV can be due to both sympathetic and parasympathetic mechanisms. Five healthy volunteers completed three pharmacological blockade sessions (placebo, sympathetic blockade with Esmolol, and parasympathetic blockade with Glycopyrrolate) about 48 hours apart, and during each session completed 11 Sudarshan Kriya Yogic breathing exercises at 4-9 BrPM. HRV was the lowest under Glycopyrrolate (p < 0.001), and there was no significant difference between placebo and sympathetic blockade with Esmolol. In addition, the spectral power of specific HRV frequencies was greatest at similar frequencies of breathing, a pattern prevented only by Glycopyrrolate. These findings suggest that heart rate is vagally influenced at all breathing rates, and that the SNS is not the mechanism by which slow breathing increases HRV.

The perception of and actual ability to control emotional responses during stressful, taxing situations are important to an individual’s well-being. Studies have shown that both low perceived control and a low actual ability for emotional control are related to internalizing and externalizing problems in youth. However, significant gaps in research exist in terms of testing theoretical predictions about how perceived and actual emotional control are associated with anxiety and aggressive behavior problems, particularly among adolescents. The first goal of this study was to examine two objective measures of actual control (i.e., vagal tone and vagal regulation) and their link with anxiety and aggressive behavior problems in youth ages 11-17 years. The second goal was to examine individual differences in youths’ ability to voluntarily control their heart rate and its association with youths’ perceived control and/or anxiety and aggressive behavior. The final goal was to expand upon Scott and Weems’ (2010) recent work by testing an adapted model of control using these two measures of actual emotional control. Eighty youth (aged 11-17 years; 51% female; 37.5% African American) and their primary caregivers participated in this study. Youth completed a physiological assessment in which they watched a relaxing video, rested quietly, increased and decreased their heart rate, and performed a mildly challenging cognitive task while their heart rate, skin conductance and body temperature were measured. Youth and their caregivers also completed questionnaires measuring youths’ anxiety, aggression, and perceived control. The results indicated that resting vagal tone (i.e., high frequency – heart rate variability) was negatively associated with anxiety symptoms (and perceived anxiety control) in this adolescent sample but not aggression. Conversely, anxiety (child-reported) and aggression (parent-reported) were both associated with a maladaptive vagal augmentation in response to a challenging cognitive task. The findings also suggested there were individual differences in youths’ heart rate control (but were better at increasing it) and that less change in increasing heart rate was related to more child-reported anxiety symptoms. However, the results did not provide support for differential of prediction of anxiety symptoms versus aggressive behavior problems between control profiles.

Research indicates that learning how to regulate one’s emotions is critical to successful child development and is associated with adaptive social functioning and psychological adjustment (Dunn & Brown, 1994; Eisenberg, Fabes, Guthrie, & Reiser, 2000; Eisenberg, Fabes, & Murphy, 1996). Children’s emotion regulation abilities are thought to be influenced by both child (e.g., age, temperament) and parent characteristics (e.g., parenting behaviors, parental regulation; Eisenberg, Cumberland, & Spinrad, 1998). Resting heart rate variability (HRV) has emerged as a potentially important biomarker associated with emotion regulation (Porges, 2007; Thayer & Lane, 2000); however, there are still significant gaps in research. In particular, research indicates genetic correlates associated with HRV as well as an important role of parents in children’s emotion socialization, but research has yet to establish a strong link between parent and child HRV. Theoretically, parent and child HRV may be linked but only in specific contexts. For example, parent and child resting HRV may become more or less strongly related in the context of specific parenting behaviors, but research has yet to test this hypothesis. The present study examined the association between parenting behaviors and child resting HF-HRV (i.e., high frequency HRV), the links between parent and child resting HF-HRV, and potential moderating effects of parenting behaviors on the association in youth. Additional analyses examined associations between parent and child vagal regulation. Ninety-seven youth (11-17 years) and their caregivers (n = 81) participated in a physiological assessment and completed questionnaires assessing parenting behaviors. Results indicated that parent’s inconsistent discipline and corporal punishment were negatively associated with their child’s resting HF-HRV while positive parenting and parental involvement were positively associated. Furthermore, parent’s inconsistent discipline and parent’s involvement moderated the relationship between parent and child resting HF-HRV, such that in the context of high inconsistent discipline and high parental involvement, high parent resting HF-HRV was associated with low child resting HF-HRV. Findings add to the literature by providing evidence for the role of parenting behaviors in shaping the development of children’s HF-HRV and indicating that inconsistent discipline and parental involvement may affect the entrainment of HF-HRV in parents and their adolescent children.

Pneumonia is the second leading cause of disability-adjusted life-years lost worldwide and the eighth leading cause of death in the United States. Traumatic brain injury (TBI) patients have classically been considered immunosuppressed, but recent research reported that mild head trauma patients have reduced incidence of pneumonia compared to blunt trauma patients. Using our mild TBI model followed by bacterial pneumonia, we investigated the effect of neuronal signaling on innate immune function. To test whether any mild injury primes host immune responses to pneumonia, we generated a mild tail trauma (TT) model. mTBI mice showed protection from bacterial pneumonia while TT mice did not. Using an FDA-approved neurokinin-1 receptor (NK1R) antagonist, aprepitant, we confirmed our previous findings that substance P (SP) is a key mediator of enhanced resistance to pneumonia. Blocking NK1R showed that mTBI-induced release of SP augments pulmonary neutrophil recruitment and microbicidal activity to pulmonary bacterial pathogens. In TT mice, NK1R agonism enhanced the same neutrophil functions, further supporting the hypothesis. No differences were found between mTBI and TT neutrophils’ ability to phagocytose, generate oxidative burst, or acidify phagosomes. However, neutrophils from mTBI mice produced more neutrophil extracellular traps in response to bacterial challenge. These studies show that neurokinin signaling in our model contributes to enhanced bacterial clearance. Cholinergic anti-inflammatory pathway signaling though the α7 nicotinic acetylcholine receptor (α7 nAChR) is also a critical component of improved survival. Blockade of α7 nAChR abrogated the mTBI survival benefit. Mimicking cholinergic signaling using α7 nAChR agonist recapitulated the mTBI reduced pro-inflammatory cytokine production and improved survival. No physiologic differences emerged within 24h following pneumonia, but mTBI and α7 agonist treated mice had significantly lower TNFα in bronchoalveolar fluid, suggesting reduced injurious pulmonary inflammation. However, replacing early TNFα during pneumonia did not increase mortality. Western blot analysis showed downregulation of HMGB1 release in mTBI mice, suggesting that vagal cholinergic signaling reduces late mediators of organ damage. Our experiments show that mTBI enhances resistance to pneumonia by activating the vagus nerve signaling through neurokinin and cholinergic pathways. Translation of these findings could be innovative solutions to fighting or preventing infections.

Previous research has shown that cognitive reappraisal, an emotion regulation strategy, has beneficial effects on emotion experience during strategy engagement. The present study extends this work by investigating whether cognitive reappraisal impacts the anticipation of an aversive event during, and five days following, strategy engagement. Emotion profiles, including psychophysiological and self-report indices, were also examined to assess whether reappraisal inhibits affective responses. Participants underwent habituation and simple discriminatory fear conditioning. Stimuli were pictures of a snake and a spider. Two days later participants returned to the laboratory and were either i) cued to engage in cognitive reappraisal while imagining the stimuli ii) exposed to the stimuli with no reappraisal instructions iii) exposed to the stimuli while engaging in cognitive reappraisal or iv) had an experience unrelated to the stimuli (control condition). Participants returned to the lab five days later and were exposed to both pictures paralleling initial habituation and conditioning protocols. It was found that cognitive reappraisal during exposure reduced expectancy of the UCS faster than exposure alone and resulted in lower mean skin conductance response (SCR) for those low, but not high, in fear of snakes. Five days later participants in the intervention conditions, compared to the control condition, demonstrated less anticipation of the UCS and smaller emotion-modulated startle magnitudes to the UCS. These findings suggest that cognitive reappraisal may be an effective tool for reducing anticipation of an aversive event and can result in enduring fear inhibition. This may have important implications for the treatment of individuals with anxiety disorders. The present study also examined the relationship between cardiac vagal control, indexed by respiratory sinus arrhythmia (RSA), and subsequent sympathetic arousal during fear conditioning, indexed by SCR. Results demonstrate that participants with low, compared to high, resting RSA had larger SCRs during habituation and conditioning trials. In addition, participants with lower RSA showed greater SCR reactivity following UCS presentation to both conditioned stimuli, suggesting that those with the lower RSA initially differentiated less between the UCS paired and unpaired images. These findings are consistent with theories that associate faster recovery from emotionally demanding situations with greater cardiac vagal control.

The dorsal vagal complex (DVC), containing the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMV), plays a pivotal role in autonomic regulation. Afferent fibers from peripheral organs and higher brain centers synapse in the NTS, which integrates these synaptic connections as well as information from systemically circulating hormones and metabolites. The integrated information is relayed to the dorsal motor nucleus of the vagus nerve (DMV), which in turn, projects motor fibers to elicit parasympathetic control of digestive and other viscera. Physiological functions mediated by the DVC are disrupted in diabetic patients and synaptic plasticity within the DVC has been linked to these complications. N-methyl-D-aspartic acid (NMDA) receptors have been extensively studied for their involvement in synaptic plasticity in a variety of central nervous system disorders; and their activation in the DVC modulates hepatic glucose production and feeding behavior. Although chronic disease can alter NMDA function, changes in DVC expression and/or sensitivity of NMDA receptors in diabetic states has not been addressed. Using whole cell electrophysiology, functional properties of the nuclei in the DVC were investigated in normoglycemic and type 1 diabetic mice. Preterminal NMDA (preNMDA) receptors were discovered to tonically modulate excitatory neurotransmission on terminals contacting DMV neurons. While these preNMDA receptors were not found to differentially modulate tonic excitatory neurotranmission, soma-dendritic NMDA receptor responses of NTS neurons were augmented in type 1 diabetic mice. Through the use single-cell PCR, increased NMDA receptor responses could be correlated to neurons that mediate excitatory neurotransmission and would argue that augmented NMDA receptor responses increase vagal output. In general, enhancing vagal output decreases activity of connected peripheral organs. Molecular approaches were employed to corroborate the observed functional NMDA receptors changes to their protein and mRNA expression levels. Overall, results argue that NMDA receptors are involved in synaptic plasticity in DVC of type 1 diabetic mice to enhance excitatory neurotransmission. This modulation may potentially serve as a physiological counter regulatory mechanism to control pathological disturbances of gastrointestinal homeostatic reflex responses.

abstract: This study examines the relations among three aspects of temperament (shyness, impulsivity, and effortful control), resting respiratory sinus arrhythmia (RSA) recorded during a calming film and RSA suppression during three behavioral measures of effortful control, and adjustment (anxiety and externalizing behavior) in a sample of 101 preschool-age children. Principal components analysis was used to create composites for effortful control, shyness, impulsivity, anxiety, and externalizing behavior, and hierarchical regression analysis was used to test the study hypotheses. As expected, baseline RSA was negatively related to effortful control in shy children, but was unrelated to effortful control in children who were not shy. It was hypothesized that high baseline RSA would reduce the relation between shyness and anxiety, and between impulsivity and externalizing behavior; this hypothesis was supported for externalizing behavior, but not for anxiety. The interaction between impulsivity and RSA as a predictor of externalizing was statistically independent of effortful control, indicating that these are unique effects. Finally, it was hypothesized that RSA suppression would be positively related to effortful control for children low, but not high, in shyness. There was a marginal interaction between shyness and RSA suppression, with RSA suppression marginally negatively related to EC for children low in shyness, but unrelated to effortful control for children high in shyness; the direction of this association was opposite predictions. These findings indicate that RSA is more strongly related to effortful control for children high in shyness, and that it consequently may not be appropriate to use RSA as an index of EC for all children. This study also draws attention to the need to consider the context in which baseline RSA is measured because a true baseline may not be obtained for shy children if RSA is measured in an unfamiliar laboratory context. The finding that high RSA moderated (but did not eliminate) the relation between impulsivity and externalizing behavior is consistent with the conceptualization of RSA as a measure of self-regulation, but further research is needed to clarify the mechanism underlying this effect. / Dissertation/Thesis / M.A. Psychology 2012

Submitted by Haroudo Xavier Filho (haroudo.xavierfo@ufpe.br) on 2016-01-19T17:57:46Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO CD.pdf: 1936828 bytes, checksum: e85b38a5c642269f2f8ca9447109ae2c (MD5) / Made available in DSpace on 2016-01-19T17:57:46Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO CD.pdf: 1936828 bytes, checksum: e85b38a5c642269f2f8ca9447109ae2c (MD5) Previous issue date: 2013-08-15 / CNPq / Previamente, foi mostrado por nossa equipe de pesquisa que o 1-nitro-2-feniletano (NF), o principal constituinte do óleo essencial de Aniba canellila, uma planta nativa da Amazônia, reduz a pressão arterial e possui efeitos vasorrelaxantes. Mais recentemente, foi observado que o 1-nitro-2-fenileteno (NFE), um derivado obtido de maneira sintética através de restrição conformacional da molécula do NF, possui uma potência 3 a 4 vezes maior para relaxar preparações isoladas de aorta torácica de rato em comparação ao NF (de origem natural). No presente estudo, visando melhorar a interação fármaco-receptor, nós investigamos os efeitos cardiovasculares de dois derivados do NFE, o 1-nitro-2-[(4'-metoxi)-fenil]-eteno (derivado I com grupamento metoxila) e 1-nitro-2-[(4'-dimetilamina)-fenil]-eteno (derivado II com grupamento dimetilamina) em ratos espontaneamente hipertensos. Sabe-se que os grupamentos metoxila e dimetilamina são elétron-doadores e podem alterar o aspecto eletrônico da molécula do NFE. Dados preliminares mostram que injeções intravenosas em bolus do NFE e dos derivados I e II induziram efeito hipotensor e bradicardizante bifásicos (fase 1 rápida e fase 2 mais tardia). A fase 1 da hipotensão e bradicardia tende a ser reduzida ou abolida após a bivagotomia e o tratamento perineural dos vagos com capsaicina (250 g/mL). A magnitude da segunda hipotensão (fase 2) tende a ser 3-4 vezes maior para os derivados I e II comparada ao NFE. Os dados dos experimentos in vitro mostram que derivados I e II induziram vasorrelaxamento em anéis de artéria mesentérica superior, pré-contraídas com fenilefrina (1 μM) com valores de CI50 [(média geométrica - intervalo de confiança de 95%)] de 22,41 [27,52-15,23] e 17,13 [31,29-11,82] μM, respectivamente. Estes efeitos vasorrelaxantes não foram influenciados pela remoção do endotélio vascular, portanto foram significativamente reduzidos pelo pré-tratamento com o ODQ (1H-[1,2,4]-oxadiazol-[4,3-a]-quinoxalin-1-ona, 10 μM), um inibidor da guanilato ciclase. Além disso, foi mostrado que a potência dos derivados I e II (avaliada através dos valores da CI50) em relaxar preparações de SMA de ratos SHR foi aumentada em comparação ao NFE (37,95 [95,83-17,74] μM). Apesar de que este aumento não atingiu nível de significância, é interessante correlacioná-lo com a aparente amplificação da resposta hipotensora da fase 2 induzida pelos os derivados I e II em relação ao NFE. Em conclusão, os derivados I e II, assim como o NFE, induziram um reflexo depressor e bradicardizante vago-vagal (fase 1). A hipotensão tardia (fase 2) parece ser resultante de um efeito vasodilatador por um mecanismo miogênico independente da integridade endotelial e parece envolver a participação da via guanilato ciclase/GMPc/PKG. / Previously, we showed that 1-nitro-2-pheyletane (NP), the main constituent of the essential oil of the Aniba canellila, a plant native to the Amazon, lowers blood pressure and induces vasorelaxant effects. Recently, it was reported that 1-nitro-2-phenyletene (NPE), a structural analogue of NP obtained synthetically, was more potent than NF to relax aortic ring preparations than NP (of natural origin). Here, in order to improve drug-receptor interaction, we intended to investigate the cardiovascular effects of two derivates of NPE, the 1-nitro-2-[(4'-methoxy)-phenyl]-ethene (derivate I) and 1-nitro-2-[(4'-dimethylamine)-phenyl]-ethene (derivate II) in spontaneously hypertensive rats. It is well-known that methoxy and dimethylamine groups are electron donors and can alter the electronic parameters of the molecule of NPE. The present preliminary results showed that intravenous injection of NPE induced two periods of hypotension and bradycardiac (phases 1 and 2). A phase 1 tended to be reduced or even abolished by bivagotomy and perineural treatment with capsaicin (250g/mL) and magnitude of hypotensive phase 2 induced by derivates I and II tended to be 3-4 times higher than that evoked by NPE. Derivates I and II relaxed endothelium-intact superior mesenteric artery (SMA) ring preparations pre-contracted with phenylephrine (1 M) with IC50 (geometric mean [95% confidence interval]) values of 22.41 [27.52-15.23] and 17.13 [31.29-11.82] μM, respectively). These vasorelaxant effects remained unchanged by removal of the vascular endothelium but were significantly reduced by pretreatment with ODQ (1H-[1,2,4] oxadiazol [4,3-a] quinoxalin-1-one, 10 μM), an inhibitor of guanylate cyclase. Furthermore, it was shown that potency of the derivatives I and II (as measured by IC50 values) in relaxing preparations SMA was increased when compared to that of NPE. Although this increase did not reach significance level, it is interesting to correlate it with the apparent amplification of the hypotensive phase 2 response induced by both derivatives I and II compared to that NPE. In conclusion, NPE and its two derivatives induced a vago-vagal bradycardiac and depressor reflex (phase 1). The delayed hypotension (phase 2) seems to result from a vasodilatory effect by a miogenic mechanism independent of endothelial integrity and appears to involve the participation of adenylate cyclase /cGMP/PKG pathway.

Cholinergic enzymes and muscarinic receptors in nuclei of rat medulla oblongata were examined after unilateral vagotomy to determine their association with efferent vagal neurons. Vagotomy caused an ipsilateral depletion of acetylcholinesterase from the dorsal motor nucleus of the vagus (DNV) and the nucleus ambiguus (NA). Choline acetyltransferase activity was reduced in ipsilateral DNV, nucleus tractus solitarius and rostral NA. Muscarinic receptor localization by autoradiography with [3H]quinuclidinyl benzilate (QNB) revealed marked intranuclear variations in receptor density. Vagotomy had no effect on the QNB binding pattern. Loss of cholinergic enzymes is a consistent response of motor and preganglionic autonomic neurons to axotomy. Depletion of muscarinic receptors is an additional component of axon reaction in brain stem motoneurons. Accordingly, previous studies have shown a decrease in neurotransmitter-related proteins after axotomy of motoneurons. In the present study, cholinergic enzymes were depleted from axotomized vagal neurons but receptors were not. It is concluded that muscarinic receptors in the DNV and NA are not associated with vagal efferent neurons.