No presente estudo, duas importantes situações foram abordadas no intuito de se melhor entender os mecanismos homeostáticos dos pressorreceptores na gênese da hipertrofia cardíaca em resposta à hipertensão renovascular: o efeito do tempo de clipe na artéria renal e o efeito dos níveis pressóricos e da variabilidade da pressão arterial. O curso temporal mostrou que, antes mesmo da instalação da hipertensão, há alteração da morfologia cardíaca, qual seja o desenvolvimento de uma hipertrofia ventricular excêntrica e, como forma de mecanismo compensatório, um aumento da expressão de algumas proteínas da homeostase do cálcio (fosfolambam fosforilada pela serina-16 e corrigido pelo fosfolambam total em 100% e fosfolambam fosforilado pela treonina-17 e corrigido pelo fosfolambam total em 54%). Uma vez instalada a hipertensão, observou-se um remodelamento ventricular esquerdo para o tipo concêntrico, com prejuízo da função diastólica e um desbalanço do sistema nervoso autonômico, com aumento da atividade simpática, observado pelo aumento da razão dos componentes de baixa freqüência (LF) e alta freqüência (HF) no tacograma (0,44 ± 0,10 vs. 0,20 ± 0,03 nos controles). A análise do efeito da pressão arterial e da variabilidade da pressão arterial mostrou uma correlação positiva com o grau de hipertrofia ventricular esquerda (r=0,76, p<0,01). A secção cirúrgica dos pressorreceptores somada à implantação do clipe na artéria renal mostrou adaptações cardiovasculares em níveis semelhantes (mesmo nível de hipertensão) e, por vezes maiores (modulação simpática para o coração e para os vasos, hipertrofia ventricular esquerda e disfunção diastólica), ao grupo cuja artéria renal foi estenosada e que permaneceu com os barorreceptores intactos. Estas respostas aconteceram num período de tempo três vezes menor na ausência do barorreflexo. Tais observações ressaltam o importante efeito homeostático do barorreflexo na gênese das respostas cardíacas adaptativas à hipertensão arterial / In the present study, two important situations were observed to evaluate the role of the baroreceptors in the genesis of cardiac hypertrophy in response to hypertension: the effect of the time-course of the clip in the renal artery and the effect of the level of arterial blood pressure (ABP) and blood pressure variability (ABPV). The time-course evaluation showed that even before hypertension was installed, cardiac alterations could be observed, as a left ventricular eccentric hypertrophy. Compensatory mechanisms, such as an increase in some calcium homeosthatic proteins, could also be noticed (increase in phosphorilated phospholmaban at threonin-17 corrected by total phospholamban in 54% and increase in phosphorilated phospholmaban at serine-16 corrected by total phospholamban in 100%). However, once hypertension was established, left ventricle morphology changed to a concentric hypertrophy, accompanied by a diastolic dysfunction and enhanced sympathetic modulation, observed by relation between low-frequency component (LF) and high-frequency component (HF) at tachogram (0,44 ± 0,10 vs. 0,20 ± 0,03 in control group). ABP and ABPV analyses showed an important positive correlation with the degree of left ventricular hypertrophy (r=0,76, p<0,01). However, the absence of baroreceptors in one of the hypertensive groups, evoked the same cardiovascular alterations (same level of hypertension) or even worse (sympathetic modulation for heart and vessels, left ventricular hypertrophy and diastolic dysfunction) reached by the hypertensive baroreceptors-preserved group. These cardiovascular responses were observed in a period that correspond one third of time to the group with intact baroreflex. These observations lead us to conclude the importance of homeosthatic effects of the baroreflex in the genesis of cardiac responses to hypertension

Avaliou-se a velocidade da onda de pulso (VOP) carótido-femoral (CF) e carótido-radial (CR), por meio de técnica não-invasiva, em 14 indivíduos diabéticos do tipo 2 normotensos, A sensibilidade do barorreflexo (SBR) foi avaliada pela manobra de Valsalva e por testes com nitroglicerina e fenilefrina, durante monitorização não-invasiva batimento-a-batimento da pressão arterial. Os resultados foram comparados aos obtidos em 13 indívíduos saudáveis pareados por idade, índice de massa corporal e sexo. O grupo diabetes apresentou maiores níveis de glicose de jejum e HbA1c. As VOP CF e CR foram mais elevadas no grupo diabetes. A SBR estava reduzida nos diabéticos, nos testes com nitroglicerina, fenilefrina e, no reflexo de taquicardia da fase II da manobra de Valsalva. O aumento da VOP CF foi significativamente correlacionado à redução da SBR. Os resultados demonstram que em diabéticos do tipo 2 há maior rigidez arterial e a SBR está reduzida. A SBR é inversamente correlacionada ao aumento da rigidez arterial / Fourteen normotensive diabetic subjects were submitted to carotid-femoral (CF) and carotid-radial (CR) pulse wave velocity (PWV) analysis by non-invasive automatic device. The baroreflex sensitivity (BRS) was evaluated by Valsalva manoeuvre, phenylephrine and nitroglycerin tests during non-invasive beat-to-beat blood pressure monitoring. The data were compared with those obtained in 13 age, body mass index and sex-matched healthy subjects. The diabetes group showed a higher fasting glucose level and HbA1c. The CF PWV and CR PWV were higher in diabetic patients. The BRS was impaired in diabetic individuals in nitroglycerine and phenylephrine tests and, also, in the tachycardic reflex in phase II of Valsalva manoeuvre. The increase of CF PWV was significantly correlated to the decrease of BRS. The data demonstrated that, in diabetic normotensive individuals, arterial stiffness is increased and the BRS is impaired. The BRS is inverselly correlated to increase of aortic stiffness

Autonomic control of the heart results in variations in the intervals between heart beats, known as heart rate variability. One of the defining components of autonomic control is the baroreflex, a negative feedback controller that balances heart rate and blood pressure. The baroreflex is under constant command from the branches of the autonomic nervous system. To better understand how the autonomic nervous system commands the baroreflex, a baroreflex reflexogenic animal protocol was carried out. Heart rate variability analysis and baroreflex sensitivity were used to quantify the neural control of the heart. This thesis reconfirmed the existence of sexually dimorphic properties in the baroreflex through the use of heart rate variability analysis and baroreflex sensitivity. It was discovered that there are many caveats to utilizing heart rate variability analysis, which have to be addressed both in the experimental protocol and the signal processing technique. Furthermore, it was suggested that the slope method for quantifying baroreflex sensitivity also has many caveats, and that other baroreflex sensitivity methods are likely more optimal for quantifying sustained activation of the baroreflex. By utilizing various heart rate variability signal processing algorithms to assess autonomic tone in Sprague-Dawley rats during rest and sustained electrical activation of the baroreflex, the null hypothesis was rejected.

Modest recovery of somatic function after incomplete spinal cord injury (SCI) has been widely demonstrated. Recently we have shown that spontaneous recovery of baroreflex regulation of sympathetic activity also occurs in rats. Dietary restriction in the form of every other day fasting (EODF) has been shown to have beneficial effects on the recovery of motor function after SCI in rats. The goal of this study was to determine if EODF augments the improvement of baroreflex regulation of sympathetic activity after chronic left thoracic (T8) surgical spinal hemisection. To determine this, we performed baroreflex tests on ad-lib fed or EODF rats 1 week or 7 weeks after left T8 spinal hemisection. One week after T8 left hemisection baroreflex testing revealed that gain of baroreflex responsiveness, as well as the ability to increase renal sympathetic nerve activity (RSNA) at low arterial pressure, was significantly impaired in the ad-lib fed but not the EODF rats compared with sham lesioned control rats. However, baroreflex tests performed 7 weeks after T8 left hemisection revealed the inability of both ad-lib and EODF rats to decrease RSNA at elevated arterial pressures. While there is evidence to suggest that EODF has beneficial effects on the recovery of motor function in rats, EODF did not significantly improve the recovery of baroreflex regulation of sympathetic activity.

The neurotrophic factor neurturin is required for normal cholinergic innervation of adult mouse heart and bradycardic responses to vagal stimulation. Our goals were to determine effects of neurturin deletion on development of cardiac chronotropic and dromotropic functions, vagal baroreflex response, and cholinergic nerve density in nodal regions of postnatal mice. Experiments were performed on postnatal C57BL/6 wild-type (WT) and neurturin knockout (KO) mice. Serial electrocardiograms were recorded noninvasively from conscious pups using an ECGenie apparatus. Mice were treated with atenolol to evaluate and block sympathetic effects on heart rate (HR) and phenylephrine (PE) to stimulate the baroreflex. Immunohistochemistry was used to label cholinergic nerves in paraffin sections. WT and KO mice showed similar age-dependent increases in HR and decreases in PR interval between postnatal days (P) 2.5 and 21. Treatment with atenolol reduced HR significantly in WT and KO pups at P7.5. PE caused a reflex bradycardia that was significantly smaller in KO pups. Cholinergic nerve density was significantly less in nodal regions of P7.5 KO mice. We conclude that cholinergic nerves have minimal influence on developmental changes in HR and PR, QRS, and QTc intervals in mouse pups. However, cholinergic nerves mediate reflex bradycardia by 1 week postnatally. Deletion of neurturin impairs cholinergic innervation of the heart and the vagal efferent component of the baroreflex early during postnatal development.

Baroreflex sensitivity is impaired by diabetes mellitus. Previously, we found that diabetes induces a deficit of central mediation of baroreflex-mediated bradycardia. In this study, we assessed whether diabetes induces degeneration of the nucleus ambiguus (NA) and reduces heart rate (HR) responses to l-Glutamate (L-Glu) microinjection into the NA. FVB control and OVE26 diabetic mice (5-6 months) were anesthetized. Different doses of L-Glu (0.1-5 mM/l, 20 nl) were delivered into the left NA using a multi-channel injector. In other animals, the left vagus was electrically stimulated at 1-40 Hz (1 ms, 0.5 mA, 20 s). HR and mean arterial blood pressure (MAP) responses to L-Glu microinjections into the NA and to the electrical stimulation of the vagus were measured. The NA region was defined by tracer TMR-D injection into the ipsilateral nodose ganglion to retrogradely label vagal motoneurons in the NA. Brainstem slices at - 600, - 300, 0, + 300, and + 600 μm relative to the obex were processed using Nissl staining and the number of NA motoneurons was counted. Compared with FVB control, we found in OVE26 mice that: 1) HR responses to L-Glu injection into the NA at doses of 0.2-0.4 (mM/l, 20 nl) were attenuated (p < 0.05), but MAP responses were unchanged (p > 0.05). 2) HR responses to vagal stimulation were increased (p < 0.05). 3) The total number of NA (left and right) motoneurons was reduced (p < 0.05). Taken together, we concluded that diabetes reduces NA control of HR and induces degeneration of NA motoneurons. Degeneration of NA cardiac motoneurons may contribute to impairment of reflex-bradycardia in OVE26 diabetic mice.

Previously, we have shown that chronic intermittent hypoxia (CIH) impairs baroreflex control of heart rate and augments aortic baroreceptor afferent function. In the present study, we examined whether CIH induces structural changes of aortic afferent axons and terminals. Young-adult Fischer 344 (F344, 4 months old) rats were exposed to room air (RA) or CIH for 35-45 days. After 14-24 days of exposure, they received tracer DiI injection into the left nodose ganglion to anterogradely label vagal afferent nerves. After surgery, animals were returned to their cages to continue RA or CIH exposure. Twenty-one days after DiI injection, the animals were sacrificed and the aortic arch was examined using confocal microscopy. In both RA and CIH rats, we found that DiI-labeled vagal afferent axons entered the wall of the aortic arch, then fanned out and branched into large receptive fields with numerous terminals (flower-sprays, end-nets and free endings). Vagal afferent axons projected much more to the anterior wall than to the posterior wall. In general, the flower-sprays, end-nets and free endings were widely and similarly distributed in the aortic arch of both groups. However, several salient differences between RA and CIH rats were found. Compared to RA control, CIH rats appeared to have larger vagal afferent receptive fields. The CIH rats had many abnormal flower-sprays, end-nets, and free endings which were intermingled and diffused into "bush-like" structures. However, the total number of flower-sprays was comparable (P>0.05). Since there was a large variance of the size of flower-sprays, we only sampled the 10 largest flower-sprays from each animal. CIH substantially increased the size of large flower-sprays (P<0.01). Numerous free endings with enlarged varicosities were identified, resembling axonal sprouting structures. Taken together, our data indicate that CIH induces significant remodeling of afferent terminal structures in the aortic arch of F344 rats. We suggest that such an enlargement of vagal afferent terminals may contribute to altered aortic baroreceptor function following CIH.

No description available.

<p>Results from this study show a moderate association between decentering and sBRS.</p> <p> Previous studies have associated decentering, a non-judgmental view of emotions, with lower arterial stiffness and better nocturnal blood pressure dipping in adults. It is unknown however if autonomic regulation of blood pressure is linked to decentering. Therefore, the purpose of this study was to determine if decentering was related to cardiovagal or sympathetic baroreflex sensitivity (sBRS). Thirty-three adults (age 25±6 years; BMI 25±3 kg/m2 ) with resting blood pressure ≥120/80 mmHg volunteered for this study. All participants had a BMI <30 kg/m2 , and had no history of smoking, diabetes, or prescriptions for blood pressure or cardiac function. Participants completed an 11-item experiences questionnaire to evaluate decentering, and then were equipped for a supine autonomic evaluation. The autonomic evaluation included continuous recording of heart rate via 3-lead ECG, muscle sympathetic nerve activity (MSNA) via microneurography, and beat-to-beat blood pressure via finger photoplethysmography. Cardiovagal baroreflex sensitivity (n=33) included estimation of vagal activation by evaluating up-up relationships between systolic arterial pressure (SAP) and R-R intervals of the ECG. Vagal withdrawal was also estimated via the down-down relationships between SAP and R-R intervals. Spontaneous sBRS (n=17) was evaluated by assessing the relationship between changes in diastolic arterial pressure (DAP) in 3 mmHg bins vs. changes in MSNA burst incidence (bursts / 100 heart beats) in those with DAP-MSNA correlations >0.70. Results from 2-tailed Pearson correlation analyses revealed that there was not a relationship between decentering and vagal activation (r=-0.07; p=0.71) or between decentering and vagal withdrawal (r=-0.28; p=0.12). There was a moderate, negative correlation between decentering and sBRS that lacked statistical significance (r= -0.35; p=0.17). Our findings suggest that there is not a clear link between decentering and autonomic regulation of blood pressure as estimated through cardiovagal 11 baroreflex sensitivity, but the moderate correlation between decentering and sBRS should be explored in a larger sample size. </p>

Cocaine- and amphetamine-regulated transcript (CART) was first identified in the rat striatum where levels were upregulated following cocaine or amphetamine administration. A dense plexus of CART-immunoreactive fibers is noted in the nucleus of the solitary tract (NTS). Results from tract-tracing and immunohistochemical studies suggest that the dense network of CARTp-fibers in the NTS may arise from nodose ganglia. The present study was undertaken to evaluate the hypothesis that CARTp may alter baroreceptor function in rats. Rats were intravenously administered phenylephrine every 10 min to elicit a baroreflex. CARTp (0.1- 3 nmol) by intracisternal or bilateral intra-NTS microinjection consistently attenuated the phenylephrineinduced bradycardia. In contrast, CARTp antibody potentiated the bradycardia produced from phenylephrine. Microinjection of saline, normal rabbit serum, or concomitant injection of CARTp and CART antibody into the NTS caused no significant change of phenylephrineinduced baroreflex. The result suggests that CARTp released from primary afferents may modulate baroreflex.