Comportamento do ergorreflexo na insuficiência cardíaca / Ergoreflex activity in heart failure / Comportamiento del ergorreflejo en la insuficiencia cardiaca

Grande número de evidências tem sugerido a existência de uma rede de reflexos que se tornam hiperativos secundariamente a alterações músculo-esqueléticas que ocorrem na síndrome insuficiência cardíaca (IC). Estes, aliados aos reflexos cardiovasculares simpato-inibitórios, suprimidos na síndrome, podem contribuir para a intolerância ao exercício físico. A hiperativação dos sinais originados dos receptores localizados nos músculos esqueléticos (mecanoceptores - metaborreceptores) é uma hipótese proposta recentemente para explicar a origem dos sintomas de fadiga e dispneia e os efeitos benéficos do treinamento físico na síndrome da IC. Na IC, outras alterações nos sistemas de controle reflexo, que não são mutuamente exclusivos, contribuem para dispneia. Estimulação inapropriada dos barorreceptores arteriais com consequente falta de inibição da descarga do metaborreflexo muscular e quimiorreflexo carotídeo e aumento da vasoconstricção renal com liberação de angiotensina II pode também ser considerada. Apesar das alterações funcionais dos reflexos terem sido usadas de maneira independente para ilustrar a excitação simpática observada na IC, a interação entre esses reflexos em condições normais e patológicas, especialmente sua contribuição para o estado simpato-excitatório encontrado na IC, não tem sido amplamente estudados. Assim, o problema se ambos os receptores musculares (mecano e metaborreceptores) estão envolvidos na gênese da exacerbação do ergorreflexo observado na IC ainda fica a ser resolvido. Dessa forma, essa revisão tem por objetivo integrar os conhecimentos a respeito do mecano e metaborreflexo (ergorreflexo) na síndrome da insuficiência cardíaca bem como esclarecer a influência da terapêutica medicamentosa da IC no ergorreflexo.

A large body of evidence has suggested the existence of a reflex network that becomes hyperactive secondary to musculoskeletal alterations that occur in heart failure (HF) syndrome. Together with sympathoinhibitory cardiovascular reflexes, suppressed in the presence of the syndrome, heart failure can contribute to physical exercise intolerance. The hyperactivation of signals originated from receptors located in skeletal muscles (mechanoreceptors - metaboreceptors) is a recently proposed hypothesis to explain the origin of fatigue and dyspnea symptoms in HF. In HF, other alterations in the reflex control system, which are not mutually exclusive, contribute to dyspnea. The inappropriate stimulation of the arterial baroreceptors, with the consequent lack of inhibition of the muscle metaboreflex and carotid chemoreflex unloading and the increase in the renal vasoconstriction with angiotensin II release can also be considered. Although the functional alterations of the reflexes were used independently to illustrate the sympathetic excitation observed in HF, the interaction between these reflexes under normal and pathological conditions, especially its contribution to the sympathoexcitatory state found in HF, has not been broadly investigated. Therefore, questions about a possible association between the muscle receptors (mechano and metaboreceptors) in the genesis of the ergoreflex exacerbation, observed in HF, remain. Thus, the objective of this review was to integrate the knowledge on the mechano and metaboreflex (ergoreflex) in HF syndrome, as well as to clarify the influence of HF drug therapy on the ergoreflex.

Gran número de evidencias viene sugerido la existencia de una red de reflejos que se hacen hiperactivos secundariamente a alteraciones musculoesqueléticas que se producen en el síndrome de la insuficiencia cardiaca (IC). Aliada a los reflejos cardiovasculares simpatoinhibitorios, suprimidos en el síndrome, la insuficiencia cardiaca puede contribuir a la intolerancia al ejercicio físico. La hiperactivación de los señales originados de los receptores ubicados en los músculos esqueléticos (mecanorreceptores - metaborreceptores) es una hipótesis propuesta recientemente para explicar el origen de los síntomas de fatiga y disnea y de los efectos benéficos del entrenamiento físico en el síndrome de IC. En la IC, otras alteraciones en los sistemas de control reflejo, que no son mutuamente exclusivos, contribuyen a la disnea. Estimulación inapropiada de los barorreceptores arteriales, con consecuente falta de inhibición de la descarga del metaborreflejo muscular y quimiorreflejo carotídeo, y el aumento de la vasoconstricción renal con liberación de angiotensina II se pueden también tener en cuenta. A pesar de las alteraciones funcionales de los reflejos haber sido utilizadas de manera independiente para ilustrar la excitación simpática observada en la IC, la interacción entre estos reflejos en condiciones normales y patológicas, especialmente su contribución para el estado simpatoexcitatorio encontrado en la IC, no viene siendo ampliamente estudiada. De este modo, resta todavía un cuestionamiento sobre la posible relación entre los receptores musculares (mecano y metaborreceptores) en la génesis de la exacerbación del ergorreflejo observado en la IC. Por tanto, esta revisión tiene por objetivo integrar los conocimientos respecto al mecano y metaborreflejo (ergorreflejo) en el síndrome de la insuficiencia cardiaca, así como aclarar la influencia de la terapéutica medicamentosa de la IC en el ergorreflejo.

Neural reflex regulation of arterial pressure in pathophysiological conditions: interplay among the baroreflex, the cardiopulmonary reflexes and the chemoreflex

The maintenance of arterial pressure at levels adequate to perfuse the tissues is a basic requirement for the constancy of the internal environment and survival.The objective of the present review was to provide information about the basic relfex mechanisms that are responsible for the moment-to-moment regulation of the cardiovascular system. We demonstrate that this control is largely provided by the action of arterial and non-arterial reflexes that detect and correct changes in arterial pressure (baroreflex), blood volume or chemical composition (mechano-and chemosensitive cardiopulmonary reflexes), and changes in bloodgas composition (chemoreceptor reflex). The importance of the integration of these cardiovascular reflexes is well understood and it is clear that processing mainly occurs in the nucleus tractus solitarii, although the mechanism is poorly understood.There are several indications that the interactions of baroreflex, chemoreflex and Bezold-Jarisch reflex inputs, and the central nervous system control the activity of autonomic preganglionic neurons through parallel afferent and efferent pathways to achieve cardiovascular homeostasis. It is surprising that so little appears in the literature about the integration of these neural reflexes in cardiovascular function. Thus, our purpose was to review the interplay between peripheral neural reflex mechanisms of arterial blood pressure and blood volume regulation in physiological and pathophysiological states. Special emphasis is placed on the experimental model or arterial hypertension induced by N-nitro-L-arginine methyl ester (L-NAME) in which the interplay of these three reflexes is demonstrable.

Autonomic processing of the cardiovascular reflexes in the nucleus tractus solitarii

The nucleus tractus solitarii (NTS) receives afferent projections from the arterial baroreceptors, carotid chemoreceptors and cardiopulmonary receptors and as a function of this information produces autonomic adjustments in order to maintain arterial blood pressure within a narrow range of variation.The activation of each of these cardiovascular afferents produces a specific autonomic response by the excitation of neuronal projections from the NTS to the ventrolateral areas of the medulla (nucleus ambiguus, caudal and rostral ventrolateral medulla). The neurotransmitters at the NTS level as well as the excitatory amino acid (EAA) receptors involved in the processing of the autonomic responses in the NTS, although extensively studied, remain to be completely elucidated. In the present review we discuss the role of the EAA L-glutamate and its different receptor subtypes in the processing of the cardiovascular reflexes in the NTS. The data presented in this review related to the neurotransmission in the NTS are based on experimental evidence obtained in our laboratory in unanesthetized rats. The two major conclusions of the present review are that a) the excitation of the cardiovagal component by cardiovascular relfex activation (chemo- and Bezold-Jarisch reflexes) or by L-glutamatae microinjection into the NTS is mediated by N-methyl-D-aspartate (NMDA) receptors, and b) the sympatho-excitatory componente of the chemoreflex and the pressor response to L-glutamate microinjected into the NTS are not affected by an NMDA receptor antagonist, suggesting that the sympatho-excitatory component of these responses is mediated by non-NMDA receptors.

Baroreflex and chemoreflex dysfunction in streptozotocin-diabetic rats

Several investigators have demonstrated that streptozotocin (STZ) diabetes induces changes in the autonomic control of the cardiovascular system. Changes in cardiovascular function may be related to peripheral neuropathy. The aim of the present study was to a changes in heart rate (HR) and arterial pressure (AP) as well as baroreflex and chemoreflex sensitivity in STZ-induced diabetic male Wistar rats (STZ, 50 mg/kg, iv, 15 days). Intra-arterial blood pressure signals were obtained for control and diabetic rats (N = 9, each group). Data were processed in a data acquisition system (CODAS, 1 kHz). Baroreflex sensitivity was evaluated by measuring heart rate changes induced by arterial pressure varíation produced by phenyiephrine and sodium nitroprusside injection. Increasing doses of potassium cyanide (KCN) were used to evaluate bradycardic and pressor responses evoked by chemoreflex activation. STZ induced hyperglycemia (447 ñ 49 vs 126 ñ 3 mg/dl), and a reduction in AP (99 + 3 vs 118 + 2mmHg), resting HR (296 ñ 11 vs 355 ñ 16 bpm) and plasma insulin levels (16 ñ 1 vs 57 + 11 muU/ml). We also observed that the reflex bradycardia (-1.68 ñ 0.1 vs -1.25 ñ 0.1 bpm/mmHg, in the diabetic group) and tachycardia (-3.68 ñ 0.5 vs -1.75 ñ 0.3 bpm/mmHg, in the diabetic group) produced by vasopressor and depressor agents were impaired in the diabetic group. Bradycardia evoked by chemoreflex activation was attenuated in diabetic rats (control: -l7 + 1,-86 + 19,-l85 ñ 18, -208 + 17 vs diabetic: -7 + 1,-23 ñ 5,-95 ñ 13, - 140 + 13 bpm), as also was the pressor response (control: 6 ñ 1,30 ñ 7,54 + 59 ñ 5 vs diabetic: 6 ñ 1,8 ñ 2,33 ñ 4,42 ñ 5 mmhg). In conclusion the cardiovascular responses evoked by baroreflex and chemoreflex activation are impaired in diabetic rats. The alterations of caradiovascular responses may be secondary to the autonomic dysfunction of cardiovascular control.

Acetate enhances the chemosensory response to hypoxia in the cat carotid body in vitro in the absence of CO2-HCO3-

To determine if intracellular acidosis enhances hypoxic chemoreception in the absence of CO2-HCO3- at pH 7.4, the effects of sodium acetate (30 mM) were studied on the chemosensory responses of the cat carotid body to hypoxic, stagnant and cytotoxic hypoxia. Carotid bodies were perfused and superfused in vitro with Tyrode's solution, free of CO2-HCO3-, buffered with HEPES-NaOH, pH 7.40, at 36.5 +/d- 0.5 degrees C and equilibrated at PO2 of 125 Torr (perfusate) and < 20 Torr (superfusate). In the absence of acetate, hypoxia (PO2 25 Torr), flow interruption and NaCN (0.01-100 micrograms) augmented the chemosensory discharges. However, in the presence of acetate, the half-excitation time of these responses decreased and their amplitude increased. Thus, acetate enhances the chemosensory response to hypoxic, stagnant and cytotoxic hypoxia. It is suggested that that intracellular acidosis induced by acetate contributes to this potentiation by correcting the alkaline pHi caused by the absence of HCO3-(-)HCO2 in the perfusate

Urinary bladder serosal chemoreceptor induced cardio-respiratory responses: possible pathway.

There is limited experimental information about pain originating from the urinary bladder. In the present study application of 3-5 ml of 1% ammonium oxalate, 1% potassium chloride, 100m M citric acid, IM ammonium chloride, 1% oxalic acid, 0.5% sodium hydroxide, or 2 micrograms/ml bradykinin, to the serosal surface of the urinary bladder in anaesthetized dogs, resulted in an increase in heart rate, rise of both systolic and diastolic blood pressures and increase in respiratory rate and depth. These facilitatory cardio-respiratory responses were coupled with powerful contractions of the urinary bladder wall. By contrast, mucosal application of the chemicals did not bring about any significant change. The cardio-respiratory responses obtained were completely abolished on serosal application of procaine (1%), section of the hypogastric nerves or by spinalectomy at T8. Bilateral cervical vagotomy and pelvic nerve section did not modify the responses. However, the blood pressure responses were abolished by the administration of tolazoline hydrochloride, indicating a major role of sympathetics in this nociceptive reflex.

Electrophysiological responses of the housefly, Musca domestica nebula (Fr), taste receptors to KCl.

This paper aims at studying the response of the housefly labellar chemoreceptor to stimulation by KCl. These studies are limited to testing various concentrations of KCl solutions (0.005-1 M), using the electrophysiological "tip recording" method and examining the various spike characteristics such as threshold, phasic and tonic response, spike amplitudes, frequency and adaptation; for the anion, cation and water receptors. The large, medium and small hairs all respond to salt. The frontal large, medium and small hairs show a higher frequency response to equimolar KCl than the distal hairs. There is a bilateral symmetry in response pattern. The results are compared with the reported work on Phormia and Calliphora species. The Biedler's hypothesis is also tested for the salt receptors of Musca.