Perfil cardiovascular após a inoculação intravenosa de veneno de abelha africanizada em ratos acordados

The manifestations caused by Africanized bee stings depend on the sensitivity of the victim and the toxicity of the venom. Previous studies in our laboratory have demonstrated cardiac changes and acute tubular necrosis (ATN) in the kidney of rats inoculated with Africanized bee venom (ABV). The aim of the present study was to evaluate the changes in mean arterial pressure (MAP) and heart rate (HR) over a period of 24 h after intravenous injection of ABV in awake rats. A significant reduction in basal HR as well as in basal MAP occurred immediately after ABV injection in the experimental animals. HR was back to basal level 2 min after ABV injection and remained normal during the time course of the experiment, while MAP returned to basal level 10 min later and remained at this level for the next 5 h. However, MAP presented again a significant reduction by the 7th and 8th h and returned to the basal level by the 24th h. The fall in MAP may contribute to the pathogenesis of ATN observed. The fall in MAP probably is due to several factors, in addition to the cardiac changes already demonstrated, it is possible that the components of the venom themselves or even substances released in the organism play some role in vascular beds.As manifestações causadas por picadas de abelhas africanizadas dependem da sensibilidade da vítima e da toxicidade do veneno. Estudos anteriores em nosso laboratório mostraram alterações cardíacas e necrose tubular aguda (NTA) nos rins de ratos inoculados com veneno de abelhas africanizadas (VAA). O objetivo do presente estudo foi avaliar as alterações na pressão arterial média (PAM) e na freqüência cardíaca (FC) num período de 24 horas após a inoculação de VAA em ratos mantidos acordados. Uma redução significante na FC basal e na PAM ocorreu imediatamente após a inoculação de VAA nos animais experimentais. A FC voltou aos níveis basais 2 min após a inoculação do VAA e permaneceu nestes valores durante o restante do experimento, enquanto que a PAM voltou aos níveis basais 10 min após a inoculação e permaneceu nestes níveis pelas próximas 5 horas. Por outro lado, a PAM apresentou uma nova diminuição significante nas 7ª e 8ª horas retornando aos níveis basais na 24ª hora. A queda na PAM nos animais inoculados com VAA deve contribuir na patogênese da NTA observada nos rins destes animais. Provavelmente a queda da PAM seja multifatorial, além das alterações cardíacas já demonstradas, os próprios componentes do veneno e/ou substâncias liberadas no organismo podem atuar na resistência vascular, contribuindo para alterações na pressão arterial

Microinjection of NMDA antagonist into the NTS of conscious rats blocks the Bezold-Jarisch reflex.

The purpose of the present study was to evaluate whether or not cardiovagal excitatory and sympatho-inhibitory pathways of the Bezold-Jarischreflex at the NTS level were mediated by NMDA receptors. The Bezold-Jarischreflex was activated by intravenous (i.v.) injection of serotonin in consciousrats before and after microinjection of phosphonovaleric acid (AP-5), a selective NMDAantagonist, into the NTS. The Bezold-Jarischreflex was also activated before and after methyl-atropine (i.v.) in order to evaluate if the changes in mean arterial pressure were dependent on the bradycardic response. The data showed that AP-5 into the NTS produced a dose-dependent reduction in both bradycardic and hypotensive responses to activation of the Bezold-Jarischreflex. Methyl-atropine also blocked the bradycardic and hypotensive responses to Bezold-Jarischreflex activation. The data show that in consciousrats the cardiovagal component of the Bezold-Jarischreflex plays a major role in the cardiovascular changes produced by the activation of this reflex and suggest that the neurotransmission of the cardiovagal component of the Bezold-Jarischreflex is mediated by NMDA receptors

Microinjection of NMDA antagonist into the NTS of conscious rats blocks the Bezold-Jarisch reflex.

The purpose of the present study was to evaluate whether or not cardiovagal excitatory and sympatho-inhibitory pathways of the Bezold-Jarischreflex at the NTS level were mediated by NMDA receptors. The Bezold-Jarischreflex was activated by intravenous (i.v.) injection of serotonin in consciousrats before and after microinjection of phosphonovaleric acid (AP-5), a selective NMDAantagonist, into the NTS. The Bezold-Jarischreflex was also activated before and after methyl-atropine (i.v.) in order to evaluate if the changes in mean arterial pressure were dependent on the bradycardic response. The data showed that AP-5 into the NTS produced a dose-dependent reduction in both bradycardic and hypotensive responses to activation of the Bezold-Jarischreflex. Methyl-atropine also blocked the bradycardic and hypotensive responses to Bezold-Jarischreflex activation. The data show that in consciousrats the cardiovagal component of the Bezold-Jarischreflex plays a major role in the cardiovascular changes produced by the activation of this reflex and suggest that the neurotransmission of the cardiovagal component of the Bezold-Jarischreflex is mediated by NMDA receptors

NMDA receptors in NTS are involved in the bradycardic but not in the pressor response of chemoreflex.

Activation of carotid chemoreceptors with intravenous potassium cyanide (KCN) produces increases in arterial pressure, bradycardia, and tachypnea. In the present study, we activated carotid chemoreceptors with KCN and the neurotransmission of the chemoreceptor reflex into the commissural nucleus tractus solitarii (NTS) was blocked with phosphonovaleric acid @P-5), an N-methyl-D-aspartate (NMDA)-selective antagonist. The aim of this study was to evaluate the involvement of NMDA receptors in the cardiovascular and respiratory responses produced by chemoreceptor activation in unanesthetized rats. The pressor response to KCN was not changed after microinjection of three different doses of AP-5 into the NTS, whereas the bradycardic response was reduced in a dosedependent manner. The increase in respiratory frequency in response to carotid chemoreceptor activation was also not affected by AP-5 microinjected into the NTS. The data indicate that the activation of the cardiovagal component of the chemoreflex in the commissural NTS is mediated by NMDA receptors, whereas pressor and ventilatory responses are not

Short-term sustained hypoxia induces changes in the coupling of sympathetic and respiratory activities in rats

Individuals experiencing sustained hypoxia (SH) exhibit adjustments in the respiratory and autonomic functions by neural mechanisms not yet elucidated. In the present study we evaluated the central mechanisms underpinning the SH-induced changes in the respiratory pattern and their impact on the sympathetic outflow. Using a decerebrated arterially perfused in situ preparation, we verified that juvenile rats exposed to SH (10% O2) for 24 h presented an active expiratory pattern, with increased abdominal, hypoglossal and vagal activities during late-expiration (late-E). SH also enhanced the activity of augmenting-expiratory neurones and depressed the activity of post-inspiratory neurones of the Botzinger complex (B ¨ otC) ¨ by mechanisms not related to changes in their intrinsic electrophysiological properties. SH rats exhibited high thoracic sympathetic activity and arterial pressure levels associated with an augmented firing frequency of pre-sympathetic neurones of the rostral ventrolateral medulla (RVLM) during the late-E phase. The antagonism of ionotropic glutamatergic receptors in the BotC/RVLM abolished the late-E bursts in expiratory and sympathetic outputs of SH rats, ¨ indicating that glutamatergic inputs to the BotC/RVLM are essential for the changes in the ¨ expiratory and sympathetic coupling observed in SH rats. We also observed that the usually silent late-E neurones of the retrotrapezoid nucleus/parafacial respiratory group became active in SH rats, suggesting that this neuronal population may provide the excitatory drive essential to the emergence of active expiration and sympathetic overactivity. We conclude that short-term SH induces the activation of medullary expiratory neurones, which affects the pattern of expiratory motor activity and its coupling with sympathetic activity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system

Respiratory modulation seen in the sympathetic nerve activity (SNA) implies that the respiratory and sympathetic networks interact. During hypertension elicited by chronic intermittent hypoxia (CIH), the SNA displays an enhanced respiratory modulation reflecting strengthened interactions between the networks. In this chapter, we review a series of experimental and modeling studies that help elucidate possible mechanisms of sympatho-respiratory coupling. We conclude that this coupling significantly contributes to both the sympathetic baroreflex and the augmented sympathetic activity after exposure to CIH. This conclusion is based on the following findings. (1) Baroreceptor activation results in perturbation of the respiratory pattern via transient activation of postinspiratory neurons in the Botzinger complex (BotC). The same BotC neurons are involved in the respiratory modulation of SNA, and hence provide an additional pathway for the sympathetic baroreflex. (2) Under hypercapnia, phasic activation of abdominal motor nerves (AbN) is accompanied by synchronous discharges in SNA due to the common source of this rhythmic activity in the retrotrapezoid nucleus (RTN). CIH conditioning increases the CO2 sensitivity of central chemoreceptors in the RTN which results in the emergence of AbN and SNA discharges under normocapnic conditions similar to those observed during hypercapnia in naive animals. Thus, respiratory-sympathetic interactions play an important role in defining sympathetic output and significantly contribute to the sympathetic activity and hypertension under certain physiological or pathophysiological conditions, and the theoretical framework presented may be instrumental in understanding of malfunctioning control of sympathetic activity in a variety of disease states.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Electrophysiological properties of rostral ventrolateral medulla presympathetic neurons modulated by the respiratory network in rats

The respiratory pattern generator modulates the sympathetic outflow, the strength of which is enhanced by challenges produced by hypoxia. This coupling is due to the respiratory-modulated presympathetic neurons in the rostral ventrolateral medulla (RVLM), but the underlining electrophysiological mechanisms remain unclear. For a better understanding of the neural substrates responsible for generation of this respiratory-sympathetic coupling, we combined immunofluorescence, single cell qRT-pCR, and electrophysiological recordings of the RVLM presympathetic neurons in in situ preparations from normal rats and rats submitted to a metabolic challenge produced by chronic intermittent hypoxia (CIH). Our results show that the spinally projected cathecholaminergic C1 and non-C1 respiratory-modulated RVLM presympathetic neurons constitute a heterogeneous neuronal population regarding the intrinsic electrophysiological properties, respiratory synaptic inputs, and expression of ionic currents, albeit all neurons presented persistent sodium current-dependent intrinsic pacemaker properties after synaptic blockade. A specific subpopulation of non-C1 respiratory-modulated RVLM presympathetic neurons presented enhanced excitatory synaptic inputs from the respiratory network after CIH. This phenomenon may contribute to the increased sympathetic activity observed in CIH rats. We conclude that the different respiratory-modulated RVLM presympathetic neurons contribute to the central generation of respiratory-sympathetic coupling as part of a complex neuronal network, which in response to the challenges produced by CIH contribute to respiratory-related increase in the sympathetic activity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES