Chronic absence of baroreceptor inputs prevents training-induced cardiovascular adjustments in normotensive and spontaneously hypertensive rats

We investigate whether arterial baroreceptors mediate the training-induced blood pressure fall and resting bradycardia in hypertensive (SHR) and normotensive rats (WKY). Male SHR and WKY rats, submitted to sino-aortic denervation (SAD) or sham surgery (SHAM group), were allocated to training (T; 55% of maximal exercise capacity) or sedentary (S) protocols for 3 months. Rats were instrumented with arterial and venous catheters for haemodynamic measurements at rest (power spectral analysis) and baroreceptor testing. Kidney and skeletal muscles were processed for morphometric analysis of arterioles. Elevated mean arterial pressure (MAP) and heart rate (HR) in SHAM SHRS were accompanied by increased sympathetic variability and arteriolar wall/lumen ratio [+3.4-fold on low-frequency (LF) power and +70%, respectively, versus WKYS, P < 0.05]. Training caused significant HR (similar to 9% in WKY and SHR) and MAP reductions (-8% in the SHR), simultaneously with improvement of baroreceptor reflex control of HR (SHR and WKY), LF reduction (with a positive correlation between LF power and MAP levels in the SHR) and normalization of wall/lumen ratio of the skeletal muscle arterioles (SHR only). In contrast, SAD increased pressure variability in both strains of rats, causing reductions in MAP (-13%) and arteriolar wall/lumen ratio (-35%) only in the SHRS. Training effects were completely blocked by SAD in both strains; in addition, after SAD the resting MAP and HR and the wall/lumen ratio of skeletal muscle arterioles were higher in SHRT versus SHRS and similar to those of SHAM SHRS. The lack of training-induced effects in the chronic absence of baroreceptor inputs strongly suggests that baroreceptor signalling plays a decisive role in driving beneficial training-induced cardiovascular adjustments.

HISTAMINE IN THE POSTERODORSAL MEDIAL AMYGDALA MODULATES CARDIOVASCULAR REFLEX RESPONSES IN AWAKE RATS

Centrally injected histamine (HA) affects heart rate (HR), arterial blood pressure (BP), and sympathetic activity in rats. The posterodorsal medial amygdala (MePD) has high levels of histidine decarboxylase, connections with brain areas involved with the modulation of cardiovascular responses, and is relevant for the pathogenesis of hypertension. However, there is no report demonstrating the role of the MePD histaminergic activity on the cardiovascular function in awake rats. The alms of the present work were: 1) to study the effects of two doses (10-100 nM) of HA microinjected in the MePD on basal cardiovascular recordings and on baroreflex- and chemoreflex-mediated responses; 2) to reveal whether cardiovascular reflex responses could be affected by MePD microinjections of (R)-alpha-methylhistamine (AH(3)), an agonist of the inhibitory autoreceptor H(3); and, 3) to carry out a power spectral analysis to evaluate the contribution of the sympathetic and parasympathetic components in the variability of the HR and BP recordings. When compared with the control group (microinjected with saline, 0.3 mu l), HA (10 nM) promoted an increase in the MAP(50), i.e. the mean value of BP at half of the HR range evoked by the baroreflex response. Histamine (100 nM) did not affect the baroreflex activity, but significantly decreased the parasympathetic component of the HR variability, increased the sympathetic/parasympathetic balance at basal conditions (these two latter evaluated by the power spectral analysis), and promoted an impairment in the chemoreflex bradycardic response. Microinjection of AH(3) (10 mu M) led to mixed results, which resembled the effects of both doses of HA employed here. Present data suggest that cardiovascular changes induced by baroreceptors and chemoreceptors involve the histaminergic activity in the MePD. This neural regulation of reflex cardiovascular responses can have important implications for homeostatic and allostatic conditions and possibly for the behavioral displays modulated by the rat MePD. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

Background: The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. Methods: Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2) in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR) similar to 250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD) or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA) were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP) and heart rate variability (spectral analysis) one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting). Results: Higher glycemia (p < 0.05) and lower mean AP were observed in diabetics vs. nondiabetics (p < 0.05). Heart rate was higher in renal-denervated hypertensive and lower in diabetic-hypertensive rats (384.8 +/- 37, 431.3 +/- 36, 316.2 +/- 5, 363.8 +/- 12 bpm in SHR, RD-SHR, STZ-SHR and RD-STZ-SHR, respectively). Heart rate variability was higher in renal-denervated diabetic-hypertensive rats (55.75 +/- 25.21, 73.40 +/- 53.30, 148.4 +/- 93 in RD-SHR, STZ-SHR-and RD-STZ-SHR, respectively, p < 0.05), as well as the LF component of AP variability (1.62 +/- 0.9, 2.12 +/- 0.9, 7.38 +/- 6.5 in RD-SHR, STZ-SHR and RD-STZ-SHR, respectively, p < 0.05). GLUT2 renal content was higher in all groups vs. SHR. Conclusions: Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.

Cardiovascular effects of acetylcholine microinjection into the ventrolateral and dorsal periaqueductal gray of rats

In the present study, we describe the cardiovascular effects of local acetylcholine (Ach) microinjection into both the ventrolateral (vlPAG) and dorsal (dPAG) periaqueductal gray areas of anesthetized rats and the possible local receptors involved with these responses. Microinjection of Ach (9, 27, 45 or 81 nmol/50 nL) into the vlPAG caused dose-related depressor responses. These hypotensive responses were blocked by local pretreatment with increasing doses of the nonselective muscarinic antagonist atropine (1, 3 or 9 nmol/50 nL). The microinjection of Ach into the dPAG caused no significant cardiovascular responses in anesthetized rats. In conclusion, the present findings suggest that a cholinergic system present in the vlPAG, but not in the dPAG, is involved with cardiovascular system control. Moreover, these cardiovascular responses evoked by Ach are mediated by muscarinic receptors. (C) 2010 Elsevier B.V. All rights reserved.

N-Methyl-D-aspartate glutamate receptors in the hypothalamic paraventricular nucleus modulate cardiac component of the baroreflex in unanesthetized rats

In the present study, we investigated the role played by the hypothalamic paraventricular nucleus (PVN) in the modulation of cardiac baroreflex activity in unanesthetized rats. Bilateral microinjections of the nonselective neurotransmission blocker CoCl(2) into the PVN decreased the reflex bradycardic response evoked by blood pressure increases, but had no effect on reflex tachycardia evoked by blood pressure decreases. Bilateral microinjections of the selective NMDA glutamate receptor antagonist LY235959 into the PVN caused effects that were similar to those observed after microinjections of CoCl(2), decreasing reflex bradycardia without affecting tachycardic response. The microinjection of the selective non-NMDA glutamate receptor antagonist NBQX into the PVN did not affect the baroreflex activity. Also, the microinjection of L-glutamate into the PVN increased the reflex bradycardia, an effect opposed to that observed after PVN treatment with CoCl(2) or LY235959, and this effect of L-glutamate was blocked by PVN pretreatment with LY235959. LY235959 injected into the PVN after iv. treatment with the selective beta(1)-adrenoceptor antagonist atenolol still decreased the reflex bradycardia. Taken together, our results suggest a facilitatory influence of the PVN on the bradycardic response of the baroreflex through activation of local NMDA glutamate receptors and a modulation of the cardiac parasympathetic activity. (C) 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Effect of acute restraint stress on the tachycardiac and bradycardiac responses of the baroreflex in rats

In the present study, we evaluated cardiac baroreflex responses of rats submitted to acute restraint stress. The baroreflex was tested: immediately before, during a 30 min exposure to restraint stress, as well as 30 and 60 min after ending the stress session (recovery period). Restraint increased both mean arterial pressure (MAP) and heart rate (HR). The magnitude of tachycardiac responses evoked by intravenous infusion of sodium nitroprusside was higher during restraint stress, whereas that of bradycardiac responses evoked by intravenous infusion of phenylephrine was decreased. Restraint-evoked baroreflex changes were still observed at 30 min into the recovery period, although MAP and HR values had already returned to control values. The baroreflex was back to control values at 60 min of the recovery period. Intravenous administration of the selective beta(1)-adrenoceptor antagonist atenolol blocked the restraint-evoked increase in the tachycardiac baroreflex response, but did not affect the effects on the bradycardiac response. In conclusion, the present results suggest that psychological stresses, such as those resulting from acute restraint, affect the baroreflex. Restraint facilitated the tachycardiac baroreflex response and reduced the bradycardiac response. Restraint-related effects on baroreflex persisted for at least 30 min after ending restraint, although MAP and HR had already returned to control levels. The cardiac baroreflex returned to control values 60 min after the end of restraint, indicating non-persistent effects of acute restraint on the baroreflex. Results also indicate that the influence of restraint stress on the baroreflex tachycardiac response is mainly dependent on cardiac sympathetic activity, whereas the action on the bradycardiac response is mediated by the cardiac parasympathetic component.

The variability of baroreflex sensitivity in juvenile, spontaneously hypertensive rats

In this study the baroreflex sensitivity of conscious, juvenile, spontaneously hypertensive rats (SHRs) was compared. The study population consisted of 19 eight-week-old male SHRs. The baroreflex sensitivity was quantified as the derivative of the variation in heart rate (HR) and the variation of mean arterial pressure (baroreflex sensitivity = Delta HR/Delta MAP). MAP was manipulated with sodium nitroprusside (SNP) and phenylephrine (PHE), administered via an inserted cannula in the right femoral vein. The SHRs were divided into four groups: (1) low bradycardic baroreflex (LB) where the baroreflex gain (BG) was between 0 and 1 bpm/mmHg with PHE; (2) high bradycardic baroreflex (HB), where the BG was < -1 bpm/mmHg with PHE; (3) low tachycardic baroreflex (LT) where the BC was between 0 and 3 bpm/mmHg with SNP; (4) high tachycardic baroreflex (HT) where the BG was > 3 bpm/mmHg with SNP. We noted that 36.8% of the rats presented with an increased bradycardic reflex, while 27.8% demonstrated an attenuated tachycardic reflex. No significant alterations were noted regarding the basal MAP and HR. There were significant differences in the baroreflex sensitivity between SHRs in the same laboratory. One should be careful when interpreting studies employing the SHR as a research model.

Important GABAergic mechanism within the NTS and the control of sympathetic baroreflex in SHR

Inhibitory neurotransmission has an important role in the processing of sensory afferent signals in the nucleus of the solitary tract (NTS), particularly in spontaneously hypertensive rats (SHR). In the present study, we tested the hypothesis that gamma-aminobutyric acid (GABA) mediated neurotransmission within the NTS produces an inhibition of the baroreflex response of splanchnic sympathetic nerve discharge (sSND). In urethane-anesthetized, artificially ventilated and vagotomized male SHR and Wistar Kyoto (WKY) rats we compared baroreflex-response curves evoked after bilateral injections into the NTS of the GABA-A antagonist bicuculline (25 pmol/50 nl) or the GABA-B antagonist CGP 35348 (5 nmol/50 nl). Baseline MAP in SHR was higher than the WKY rats (SHR: 153+/-5, vs. WKY: 112+/-6 mm Hg, p<0.05). Bilateral injection of bicuculline or CGP 35348 into the NTS induced a transient (5 min) reduction in MAP (Delta = -26+/-4 and -41+/-6 mm Hg, respectively vs. saline Delta = +4+/-3 mm Hg, p<0.05) and sSND (Delta = -21+/-13 and -78+/-7%, respectively vs. saline: Delta = +6+/-4% p<0.05). Analysis of the baroreceptor curve revealed a decrease in the lower plateau (43+/-11 and 15+/-5%, respectively vs. saline: 78+/-6%, p<0.05) and an increase in the sympathetic gain of baroreflex (6.3+/-0.3, 7.2+/-0.8% respectively vs. saline: 4.2+/-0.4%, p<0.05). Bicuculline or CGP35348 into the NTS in WKY rats did not change MAP, sSND and sympathetic baroreflex gain. These data indicate that GABAergic mechanisms within the NTS act tonically reducing sympathetic baroreflex gain in SHR. Crown Copyright (C) 2010 Published by Elsevier By. All rights reserved.

Effect of baroreceptor denervation on the autonomic control of arterial pressure in conscious mice

This study evaluated the role of arterial baroreceptors in arterial pressure (AP) and pulse interval (PI) regulation in conscious C57BL mice. Male animals, implanted with catheters in a femoral artery and a jugular vein, were submitted to sino-aortic (SAD), aortic (Ao-X) or carotid sinus denervation (Ca-X), 5 daysprior to the experiments. After basal recording of AP, the lack of reflex bradycardia elicited by administration of phenylephrine was used to confirm the efficacy of SAD, and cardiac autonomic blockade with methylatropine and propranolol was performed. The AP and PI variability were calculated in the time and frequency domains (spectral analysis/fast Fourier transform) with the spectra quantified in low-(LF; 0.25-1Hz) and high-frequency bands (HF; 1-5Hz). Basal AP and AP variability were higher after SAD, Ao-X or Ca-X than in intact mice. Pulse interval was similar among the groups, whereas PI variability was lower after SAD. Atropine elicited a slight tachycardia in control mice but did not change PI after total or partial denervation. The bradycardia caused by propranolol was higher after SAD, Ao-X or Ca-X compared with intact mice. The increase in the variability of AP was accompanied by a marked increase in the LF and HF power of the AP spectra after baroreceptor denervation. The LF and HF power of the PI were reduced by SAD and by Ao-X or Ca-X. Therefore, both sino-aortic and partial baroreceptor denervation in mice elicits hypertension and a remarkable increase in AP variability and cardiac sympathetic tonus. Spectral analysis showed an important contribution of the baroreflex in the power of LF oscillations of the PI spectra. Both sets of baroreceptors seem to be equally important in the autonomic regulation of the cardiovascular system in mice.

A method to estimate EMG crosstalk between two muscles based on the silent period following an H-reflex

The crosstalk phenomenon consists in recording the volume-conducted electromyographic activity of muscles other than that under study. This interference may impair the correct interpretation of the results in a variety of experiments. A new protocol is presented here for crosstalk assessment between two muscles based on changes in their electrical activity following a reflex discharge in one of the muscles in response to nerve stimulation. A reflex compound muscle action potential (H-reflex) was used to induce a silent period in the muscle that causes the crosstalk, called here the remote muscle. The rationale is that if the activity recorded in the target muscle is influenced by a distant source (the remote muscle) a silent period observed in the electromyogram (EMG) of the remote muscle would coincide with a decrease in the EMG activity of the target muscle. The new crosstalk index is evaluated based on the root mean square (RMS) values of the EMGs obtained in two distinct periods (background EMG and silent period) of both the remote and the target muscles. In the present work the application focused on the estimation of the degree of crosstalk from the soleus muscle to the tibialis anterior muscle during quiet stance. However, the technique may be extended to other pairs of muscles provided a silent period may be evoked in one of them. (C) 2009 IPEM. Published by Elsevier Ltd. All rights reserved.

Catheter ablation of severe neurally meditated reflex (neurocardiogenic or vasovagal) syncope: cardioneuroablation long-term results

Aims Neurally meditated reflex or neurocardiogenic or vasovagal syncope (NMS) is usually mediated by a massive vagal reflex. This study reports the long-term outcome of NMS therapy based on endocardial radiofrequency (RF) catheter ablation of the cardiac vagal nervous system aiming permanent attenuation or elimination of the cardioinhibitory reflex (cardioneuroablation). Methods and results A total of 43 patients (18F/25M, 32.9+/-15 years) without apparent cardiopathy (left ventricular ejection fraction=68.6+/-5%) were included. All had recurrent NMS (4.7+/-2 syncope/patient) with important cardioinhibition (pauses=13.5+/-13 s) at head-up tilt test (HUT), normal electrocardiogram (ECG), and normal atropine test (AT). The patients underwent atrial endocardial RF ablation using spectral mapping to track the neurocardiac interface (AF Nest Mapping). The follow-up (FU) consisted of clinical evaluation, ECG (1 month/every 6 months/or symptoms), Holter (every 6 months/or symptoms), HUT (>= 4 months/or symptoms), and AT (end of ablation and >= 6 months). A total of 44 ablations (48+/-9 points/patient) were performed. Merely three cases of spontaneous syncope occurred in 45.1+/-22 months (two vasodepressor, one undefined). Only four partial cardioinhibitory responses occurred in post-ablation HUT without pauses or asystole (sinus bradycardia). Long-term AT (21.7+/-11 months post) was negative in 33 (76.7%, P<0.01), partially positive in 7(16.3%), and normal in three patients only (6.9%) reflecting long-term vagal denervation (AT-Delta% HR pre 79.4% x 23.2% post). The post-ablation stress test and Holter showed no abnormalities. No major complications occurred. Conclusion Endocardial RF catheter ablation of severe neurally meditated reflex syncope prevented pacemaker implantation and showed excellent long-term results in well selected patients. Despite no action in vasodepression it seems to cause enough long-term vagal reflex attenuation, eliminating the cardioinhibition, and keeping most patients asymptomatic. Indication was based on clinical symptoms, reproduction of severe cardioinhibitory syncope, and normal atropine response.

Hemodynamic responses to aortic depressor nerve stimulation in conscious L-NAME-induced hypertensive rats

Durand MT, Castania JA, Fazan R Jr, Salgado MC, Salgado HC. Hemodynamic responses to aortic depressor nerve stimulation in conscious L-NAME-induced hypertensive rats. Am J Physiol Regul Integr Comp Physiol 300: R418-R427, 2011. First published November 24, 2010; doi: 10.1152/ajpregu.00463.2010.-The present study investigated whether baroreflex control of autonomic function is impaired when there is a deficiency in NO production and the role of adrenergic and cholinergic mechanisms in mediating reflex responses. Electrical stimulation of the aortic depressor nerve in conscious normotensive and nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats was applied before and after administration of methylatropine, atenolol, and prazosin alone or in combination. The hypotensive response to progressive electrical stimulation (5 to 90 Hz) was greater in hypertensive (-27 +/- 2 to -64 +/- 3 mmHg) than in normotensive rats (-17 +/- 1 to -46 +/- 2 mmHg), whereas the bradycardic response was similar in both groups (-34 +/- 5 to -92 +/- 9 and -21 +/- 2 to -79 +/- 7 beats/min, respectively). Methylatropine and atenolol showed no effect in the hypotensive response in either group. Methylatropine blunted the bradycardic response in both groups, whereas atenolol attenuated only in hypertensive rats. Prazosin blunted the hypotensive response in both normotensive (43%) and hypertensive rats (53%) but did not affect the bradycardic response in either group. Prazosin plus angiotensin II, used to restore basal arterial pressure, provided hemodynamic responses similar to those of prazosin alone. The triple pharmacological blockade abolished the bradycardic response in both groups but displayed similar residual hypotensive response in hypertensive (-13 +/- 2 to -27 +/- 2 mmHg) and normotensive rats (-10 +/- 1 to -25 +/- 3 mmHg). In conclusion, electrical stimulation produced a well-preserved baroreflex-mediated decrease in arterial pressure and heart rate in conscious L-NAME-induced hypertensive rats. Moreover, withdrawal of the sympathetic drive played a role in the reflex bradycardia only in hypertensive rats. The residual fall in pressure after the triple pharmacological blockade suggests the involvement of a vasodilatory mechanism unrelated to NO or deactivation of alpha(1)-adrenergic receptor.

Modeling upper eyelid kinematics during spontaneous and reflex blinks

To test a mathematical model for measuring blinking kinematics. Spontaneous and reflex blinks of 23 healthy subjects were recorded with two different temporal resolutions. A magnetic search coil was used to record 77 blinks sampled at 200 Hz and 2 kHz in 13 subjects. A video system with low temporal resolution (30 Hz) was employed to register 60 blinks of 10 other subjects. The experimental data points were fitted with a model that assumes that the upper eyelid movement can be divided into two parts: an impulsive accelerated motion followed by a damped harmonic oscillation. All spontaneous and reflex blinks, including those recorded with low resolution, were well fitted by the model with a median coefficient of determination of 0.990. No significant difference was observed when the parameters of the blinks were estimated with the under-damped or critically damped solutions of the harmonic oscillator. On the other hand, the over-damped solution was not applicable to fit any movement. There was good agreement between the model and numerical estimation of the amplitude but not of maximum velocity. Spontaneous and reflex blinks can be mathematically described as consisting of two different phases. The down-phase is mainly an accelerated movement followed by a short time that represents the initial part of the damped harmonic oscillation. The latter is entirely responsible for the up-phase of the movement. Depending on the instantaneous characteristics of each movement, the under-damped or critically damped oscillation is better suited to describe the second phase of the blink. (C) 2010 Elsevier B.V. All rights reserved.

Avaliação manométrica anal de crianças com encoprese

INTRODUÇÃO: A constipação crônica é doença comum na infância, ocorrendo em 5 a 10% dos pacientes pediátricos, considerada a segunda maior causa de procura nos consultórios de pediatria, sendo a encoprese decorrente de constipação grave associada à impactação fecal no reto. Dentre os exames diagnósticos, a manometria anal é utilizada para a avaliação de pacientes com distúrbios funcionais, como a constipação intestinal e a incontinência fecal, em alguns serviços para a avaliação de pacientes com encoprese, pois pode trazer informações sobre o mecanismo evacuatório e possíveis lesões esfincterianas anais. OBJETIVO: Verificar alterações manométricas em pacientes com encoprese. MÉTODOS: Foi realizado estudo de 40 manometrias anais de crianças constipadas com encoprese (G1) e 12 crianças constipados sem encoprese (G2). Foram obtidos os seguintes dados: pressões de repouso, contração e evacuação do canal anal e ampola retal, ponto de maior pressão, reflexo inibitório anal e sensibilidade retal. As manometrias foram realizadas com o aparelho Alacer de perfusão com 8 canais. RESULTADOS: Não foram encontradas diferenças nas pressões de repouso, contração e evacuação do canal anal entre os grupos. Chamou-nos a atenção a ausência de necessidade de maior volume retal para desencadear o reflexo inibitório anal. Não houve diferença da incidência de anismus entre os dois grupos, demonstrando que não se trata de fator importante na manutenção da encoprese, mas sim da constipação. CONCLUSÃO: Não houve necessidade de maior volume para desencadear o reflexo inibitório anal. O anismus não foi diferente entre os dois grupos, não sendo importante na manutenção da encoprese.

Redescription of two neotropical species of Toxophora Meigen (Diptera, Bombyliidae, Toxophorinae)

Two neotropical species of Toxophora Meigen, 1848 are redescribed (T. aurea Macquart, 1848 and T. leucon Séguy, 1930) and the male terminalia, female spermathecae, and the eggs are described and illustrated. Both species can be easily segregated from the other congeners by the following features: T. leucon: body covered with dark brown scales, longitudinal stripe formed by yellow scales on center of mesonotum, scutellum and abdomen, and abdomen slender; T. aurea: antenna with short dark brown scales, body covered with yellow scales and spots of dark brown scales with greenish reflex, wings without inter-radial vein, femora with yellow scales and without setae on males, and abdomen stout.