ACE gene dosage determines additional autonomic dysfunction and increases renal angiotensin II levels in diabetic mice

OBJECTIVES: The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. METHODS: Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). Hemodynamic, cardiovascular, and autonomic parameters as well as renal Ang II expression were evaluated. RESULTS: Heart rate was lower in diabetic animals than in non-diabetic animals. Autonomic modulation analysis indicated that the 3CD group showed increased sympathetic modulation and decreased vagal modulation of heart rate variability, eliciting increased cardiac sympathovagal balance, compared with all the other groups. Concurrent diabetes and either angiotensin-converting enzyme polymorphism resulted in a significant increase in Ang II expression in the renal cortex. CONCLUSION: Data indicates that a small increase in angiotensin-converting enzyme activity in diabetic animals leads to greater impairment of autonomic function, as demonstrated by increased sympathetic modulation and reduced cardiac vagal modulation along with increased renal expression of Ang II.

The influence of distal colon irritation on the changes of cystometry parameters to esophagus and colon distentions

ABSTRACT The co-occurrence of multiple pathologies in the pelvic viscera in the same patient, such as, irritable bowel syndrome and interstitial cystitis, indicates the complexity of viscero-visceral interactions and the necessity to study these interactions under multiple pathological conditions. In the present study, the effect of distal colon irritation (DCI) on the urinary bladder interaction with distal esophagus distention (DED), distal colon distention (DCD), and electrical stimulation of the abdominal branches of vagus nerve (abd-vagus) were investigated using cystometry parameters. The DCI significantly decreased the intercontraction time (ICT) by decreasing the storage time (ST); nonetheless, DED and Abd-vagus were still able to significantly decrease the ICT and ST following DCI. However, DCD had no effect on ICT following the DCI. The DCI, also, significantly decreased the Intravesical pressure amplitude (P-amplitude) by increasing the resting pressure (RP). Although DED has no effect on the P-amplitude, both in the intact and the irritated animals, the abd-vagus significantly increased the P-amplitude following DCI by increasing the maximum pressure (MP). In the contrary, 3mL DCD significantly increased the P-amplitude by increasing the MP and lost that effect following the DCI. Concerning the pressure threshold (PT), none of the stimuli had any significant changes in the intact animals. However, DCI significantly decreased the PT, also, the abd-vagus and 3mL DCD significantly decreased the PT. The results of this study indicate that chemical irritation of colon complicates the effects of mechanical irritation of esophagus and colon on urinary bladder function.

Interval training based on ventilatory anaerobic threshold increases cardiac vagal modulation and decreases high-sensitivity c-reative protein: randomized clinical trial in coronary artery disease

Background: Autonomic dysfunction and inflammatory activity are involved in the development and progression of coronary artery disease (CAD), and exercise training has been shown to confer a cardiovascular benefit. Objective: To evaluate the effects that interval training (IT) based on ventilatory anaerobic threshold (VAT) has on heart rate variability (HRV) and high-sensitivity C-reactive protein (hs-CRP) levels, as well as the relationship between both levels, in patients with CAD and/or cardiovascular risk factors (RF). Method: Forty-two men (aged 57.88±6.20 years) were divided into two training groups, CAD-T (n= 12) and RF-T (n= 10), and two control groups, CAD-C (n= 10) and RF-C (n=10). Heart rate and RR intervals in the supine position, cardiopulmonary exercise tests, and hs-CRP levels were measured before and after IT. HRV was analyzed by spectral and symbolic analysis. The CAD-T and RF-T underwent a 16-week IT program of three weekly sessions at training intensities based on the VAT. Results: In the RF-T, cardiac sympathetic modulation index and hs-CRP decreased (p<0.02), while cardiac parasympathetic modulation index increased (p<0.02). In the CAD-T, cardiac parasympathetic modulation index increased, while hs-CRP, systolic, and diastolic blood pressures decreased (p<0.02). Both control groups showed increase in hs-CRP parameters (p<0.02). There was a strong and significant association between parasympathetic and sympathetic modulations with hs-CRP. Conclusion: The IT program based on the VAT promoted a decrease in hs-CRP associated with improvement in cardiac autonomic modulation.

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats / Mecanismos Neurais e Retardo do Esvaziamento Gástrico de Liquido Induzido no Infarto Agudo do Miocárdio em Ratos

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN. .

Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos. .

Impact of CPAP on physical exercise tolerance and sympathetic-vagal balance in patients with chronic heart failure / Impacto da CPAP sobre a tolerância ao exercício físico e a modulação simpatovagal de pacientes com insuficiência cardíaca crônica

Background: Chronic heart failure (CHF) leads to exercise intolerance. However, non-invasive ventilation is able to improve functional capacity of patients with CHF. Objectives: The aim of this study was to evaluate the effectiveness of continuous positive airway pressure (CPAP) on physical exercise tolerance and heart rate variability (HRV) in patients with CHF. Method : Seven men with CHF (62±8 years) and left ventricle ejection fraction of 41±8% were submitted to an incremental symptom-limited exercise test (IT) on the cicloergometer. On separate days, patients were randomized to perform four constant work rate exercise tests to maximal tolerance with and without CPAP (5 cmH2O) in the following conditions: i) at 50% of peak work rate of IT; and ii) at 75% of peak work rate of IT. At rest and during these conditions, instantaneous heart rate (HR) was recorded using a cardiofrequencimeter and HRV was analyzed in time domain (SDNN and RMSSD indexes). For statistical procedures, Wilcoxon test or Kruskall-Wallis test with Dunn's post-hoc were used accordingly. In addition, categorical variables were analysed through Fischer's test (p<0.05). Results: There were significant improvements in exercise tolerance at 75% of peak work rate of IT with CPAP (405±52 vs. 438±58 s). RMSSD indexes were lower during exercise tests compared to CPAP at rest and with 50% of peak work rate of IT. Conclusion: These data suggest that CPAP appears to be a useful strategy to improve functional capacity in patients with CHF. However, the positive impact of CPAP did not generate significant changes in the HRV during physical exercises. .

Contextualização: A insuficiência cardíaca (IC) crônica cursa com intolerância ao exercício físico. A ventilação não invasiva (VNI) tem se mostrado benéfica para a melhora da performance desses pacientes. Objetivos: Avaliar a eficiência da pressão positiva contínua nas vias aéreas (CPAP) sobre a tolerância ao exercício físico e a variabilidade da frequência cardíaca (VFC) de pacientes com IC crônica. Método: Sete homens com IC crônica (62±8 anos) e fração de ejeção do ventrículo esquerdo de 41±8% foram submetidos ao teste incremental (TI) sintoma-limitado em cicloergômetro. Posteriormente, foram aleatorizados para a realização de exercícios físicos de carga constante até a tolerância máxima com e sem CPAP (5 cmH2O) nas condições: i) 50% da carga pico do TI e ii) 75% da carga pico do TI. Em repouso e durante os testes, a frequência cardíaca (FC) instantânea foi obtida pelo cardiofrequencímetro, e a VFC foi analisada no domínio do tempo. A análise estatística foi realizada pelos testes de Wilcoxon ou Kruskall-Wallis com post-hoc de Dunn e as variáveis categóricas, pelo teste de Fischer (p<0,05). Resultados: Durante a CPAP, houve aumento significativo no tempo de exercício físico (405±52 vs. 438±58 s) e da FC pico (97±3 vs. 105±2 bpm) somente na intensidade de 75%. Em relação à VFC, observou-se que o RMSSD foi significativamente menor em exercício físico quando comparado ao repouso com CPAP na intensidade 50%. Conclusão: Em conclusão, a CPAP com 5 cmH20 mostrou-se um útil na melhora da capacidade funcional dos pacientes estudados com pouco impacto sobre a VFC. .

Central 5-HT2A receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats

Activation of 5-hydroxytryptamine (5-HT) 5-HT1A, 5-HT2C, 5-HT3, and 5-HT7 receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT2A/2B receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT2A/2B antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT2A antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT2B antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT2A receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT2B receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT2A receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.

Lower cardiac vagal tone in non-obese healthy men with unfavorable anthropometric characteristics

Objectives: to determine if there are differences in cardiac vagal tone values in non-obese healthy, adult men with and without unfavorable anthropometric characteristics. Introduction: It is well established that obesity reduces cardiac vagal tone. However, it remains unknown if decreases in cardiac vagal tone can be observed early in non-obese healthy, adult men presenting unfavorable anthropometric characteristics. Methods: Among 1688 individuals assessed between 2004 and 2008, we selected 118 non-obese (BMI <30 kg/m²), healthy men (no known disease conditions or regular use of relevant medications), aged between 20 and 77 years old (42 ± 12-years-old). Their evaluation included clinical examination, anthropometric assessment (body height and weight, sum of six skinfolds, waist circumference and somatotype), a 4-second exercise test to estimate cardiac vagal tone and a maximal cardiopulmonary exercise test to exclude individuals with myocardial ischemia. The same physician performed all procedures. Results: A lower cardiac vagal tone was found for the individuals in the higher quintiles - unfavorable anthropometric characteristics - of BMI (p=0.005), sum of six skinfolds (p=0.037) and waist circumference (p<0.001). In addition, the more endomorphic individuals also presented a lower cardiac vagal tone (p=0.023), while an ectomorphic build was related to higher cardiac vagal tone values as estimated by the 4-second exercise test (r=0.23; p=0.017). Conclusions: Non-obese and healthy adult men with unfavorable anthropometric characteristics tend to present lower cardiac vagal tone levels. Early identification of this trend by simple protocols that are non-invasive and risk-free, using select anthropometric characteristics, may be clinically useful in a global strategy to prevent cardiovascular disease.

Implicaciones clínicas y pronósticas del estudio circadiano de la modulación simpático-vagal de la variabilidad de la frecuencia cardiaca en pacientes con hipertensión arterial pulmonar grave / Clinical implications and prognostic significance of the study on the circadian variation of heart rate variability in patients with severe pulmonary hypertension

Introducción: La reducción en la variabilidad de la frecuencia cardiaca ha sido identificada como factor de riesgo en enfermedad cardiovascular, pero su descripción en hipertensión arterial pulmonar severa se desconoce. Material y métodos: Se estudiaron pacientes con hipertensión arterial pulmonar grave, 32 con hipertensión pulmonar primaria, 34 con hipertensión pulmonar secundaria a cardiopatía congénita (Eisenmenger) y 44 sujetos control sin evidencia de enfermedad. La evaluación del registro ambulatorio de la frecuencia cardiaca se realizó por métodos convencionales. El análisis espectral y la relación a baja y alta frecuencia se realizó utilizando el método de Fourier. Comparaciones entre día y noche se realizó entre los grupos. Después de conocer el perfil circadiano, 15 pacientes con hipertensión pulmonar fueron seleccionados para recibir tratamiento al azar con Treprostinil (Prostaglandina) o placebo por vía subcutánea. Posteriormente (3 meses) se analizaron nuevamente los parámetros de variabilidad de frecuencia cardiaca y de hemodinámica para conocer el impacto de dicha terapéutica. Resultados: Se detectó un estado franco de hipertonía simpática en el grupo de hipertensión pulmonar, sobre todo en los pacientes con hipertensión pulmonar primaria. El efecto de Treprostinil fue claramente asociado con disminución del tono simpático y un aumento de la capacidad física. Conclusiones: Los pacientes con hipertensión arterial pulmonar, cursan con equilibrio simpático-vagal alterado sobre todo durante el día. Hay pérdida del ritmo circadiano. Dichos trastornos pueden ser reversibles con la aplicación de treprostinil. El equilibrio simpáticovagal de la frecuencia cardiaca es un instrumento no invasivo que permite estratificar mejor al paciente con hipertensión arterial pulmonar grave.

BACKGROUND: A reduction of heart rate variability (HRV) is currently considered an independent risk factor for morbidity, mortality and severity of severalcardiac disease, however, the dynamic sympathovagal modulation on HRV during 24 hr in primary pulmonary hypertension (PPH) had not been described. METHODS: 24 hr Holter monitoring (HA) were recorded in 32 patients (mean age 34, +/-12, 90% female) with severe primary pulmonary hypertension (mean pulmonary pressure, 90:t:12 mm Hg), and in 34 patients (mean age 36 +/-14, 60% female) with Eisenmenger syndrome (ES) secondary to septal ventricular defect or atent ductus arteriosus. A control group (n=44) paired for age, gender and arterial pulmonary pressure was included. HRV time and spectral parameters (mean, SDNN, SDANN, rMSSD, PNN50, LF, HF and LF/HF ratio) were analyzed during three periods: 24 hr; day (8-22:00), night (23-07:00) and also every hour of recording at 5 min-intervals). After detection of sympatho-vagal balance 15 patients were randomized, Treprostinil (prostaglandin) was administered to 6 patients and subcutaneous placebo to 9. RESULTS: HRV frequency parameters during 24 hr HM were significantly different among groups. LF/HF (day) 5.9:1:12.5:1:1P.001 and LF/HF night) 2.8:tlvs.1.5:l:.8.034. Sympathovagal modulation on 24 hr HRV showed that heart rate circadian rhythm is clearly altered in both PPH and ES, but the sympathetic tone in PPH is higher at l 24 hr. (p < .05), after administering treprostinil a recovery of sympathovagal balance was observed CONCLUSIONS: Autonomic cardiac disturbance is clearly present in PPH and ES. The circadian rhythm of HRV is first lost due to an increase of sympathetic tone. These changes may be markers of autonomic disbalance that favor the development of arrhythmias and sudden death. The sympathovagal balance in PPH could be considered an important risk marker.

Active orthostatic stress and respiratory sinus arrhythmia in patients with Chagas' disease with preserved left ventricular global systolic function / Estresse ortostático ativo e arritmia sinusal respiratória em chagásicos com função sistólica global do ventrículo esquerdo preservada

OBJETIVO: Avaliar a utilização do teste de estresse ostostático ativo na detecção de disfunção vagal em chagásicos com função sistólica global preservada, comparando-o ao teste da arritmia sinusal respiratória. MÉTODO: Foram selecionados 61 chagásicos (Ch) e 38 não-chagásicos (NCh) sem evidências significativas de cardiopatia ou doenças sistêmicas, submetidos ao ecodopplercardiograma e às provas autonômicas. O teste da arritmia sinusal respiratória foi realizado através do registro eletrocardiográfico enquanto o paciente respirava profundamente, a 6 irpm, calculando-se a razão E:I (média das razões entre os maiores intervalos RR expiratórios e os menores RR inspiratórios a cada ciclo). O eletrocardiograma foi registrado enquanto o paciente se levantava e nos 30s seguintes (teste do estresse ortostático ativo), calculando-se a razão RR máx./RR min (maior e menor intervalo RR logo após a mudança postural). Os índices foram ajustados para covariáveis significativas. RESULTADOS: A razão RR max:min (NCh: 1,52 [1,44-1,74] x Ch: 1,43 [1,33-1,51], p < 0,001) e a razão E:I (NCh: 1,38±0,02 x Ch: 1,25±0,02, p<0,001) foram menores entre os chagásicos. Houve elevada correlação entre a razão RR max:min e a razão E:I ajustadas (r = 0,628, p < 0,001), mas ambas não se correlacionaram significativamente com a fração de ejeção do ventrículo esquerdo. CONCLUSAO: Chagásicos com função sistólica global do ventrículo esquerdo preservada apresentam redução significativa de índices vagais obtidos por provas curtas, quando comparados a controles normais. O teste de estresse ortostático ativo apresentou boa correlação com a manobra de arritmia sinusal respiratória, constituindo-se opção válida na avaliação ambulatorial do controle vagal.

Diabetic autonomic neuropathy causing gall bladder dysfunction.

OBJECTIVE: The objective of the study was to study gall bladder volume in fasting and 45 minutes post-prandial, by real time ultrasound in healthy controls and diabetic patients with and without autonomic neuropathy and to compare them. METHOD: Age, Sex and body mass index (BMI) matched 50 healthy subjects and 10 patients with insulin dependent diabetes mellitus and 40 patients with noninsulin dependent diabetes mellitus were evaluated according to National diabetes Data Group of National Institute of Health (1979) criteria: 1. Fasting (overnight) venous plasma glucose concentration of > 140 mg/dl on two separate occasions. 2. Following ingestion of 75 gms of glucose, venous plasma glucose concentration of > 200 mg/dl at second hour and at one other occasion during two hour test. Autonomic neuropathy was assessed by the presence of symptoms like dysphagia, abdominal fullness, nausea, vomiting, diarrhea +/- nocturnal, faecal incontinence or constipation, dysuria, urinary incontinence, the gustatory sweating, impotence etc. and were confirmed by standing test for orthostatic hypotension, hand grip test, Valsalva test and deep breaths test. RESULT: The study showed that: 1. Patients of diabetes mellitus had statistically significant larger fasting gall bladder volumes and these values were highly significant amongst patients with autonomic neuropathy. 2. Patients of diabetes mellitus and statistically significant larger post fatty meal gall bladder volume and these values were highly significant in patients with autonomic neuropathy. CONCLUSIONS: We therefore conclude that impaired gall bladder contraction was found amongst patients of diabetes mellitus with autonomic neuropathy. The mechanism responsible for cholecystoparesis is attributed to vagal neuropathy. Incomplete gall bladder emptying leads to sequestration of cholesterol and nidus formation. Therefore gall bladder functions should be evaluated routinely in such patients and early intervention is recommended.

Vagal dysfunction following endoscopic variceal sclerotherapy.

BACKGROUND: Sclerotherapy is associated with complications which involve adjacent structures like the pleura. The effect of sclerotherapy on function of the vagus nerve, which lies in close proximity to the thoracic esophagus, is not clear. AIM: To study gastric acid secretion as a marker of vagal function in portal hypertensive patients who have undergone sclerotherapy. METHODS: Portal hypertensive patients who had undergone at least three sessions of sclerotherapy were evaluated by mapping gastric acid-secreting mucosa by the Congo red test and by estimating gastric acid secretion using the modified sham feeding test. Patients with portal hypertension who had never been subjected to endoscopic sclerotherapy were recruited as controls. RESULTS: On Congo red test, complete or substantial reduction in acid-secreting mucosa was observed in eight patients in comparison to none of the controls. Significantly lower acid secretion on modified sham feeding test was observed in these eight patients. CONCLUSION: A lower gastric acid secretion, probably secondary to vagal dysfunction, is seen in patients who have undergone multiple sessions of sclerotherapy; vagus nerve involvement may be secondary to periesophageal inflammation.

Nevralgia vagoglossofaríngea / Vagoglossopharyngeal neuralgia

A revisäo dos conceitos vigentes sobre a clínica, patogenia, diagnóstico diferencial e tratamento da neuralgía vagoglossofaríngea, e relato de três casos operados por neurotomia intracraniana do n. IX e n. X (parcial). A anatomia da inervaçäo sensitiva da regiöes profundas da face e transiçäo cervicofacial, com suas implicaçöes clínicas, e a teoria da compressäo neurovascular na patogenia das disfunçöes clínicas, e a teoria da compressäo neurovascular na patogenia das disfunçöes ditas "hiperativa" dos nervos cranianos, säo comentadas criticamente

Depressed respiratory sinus arrhythmia: additional evidence for impairment of vagal activity in human hyperthyroidism

The efferent activity of the parasympathetic component of the autonomic nervous system was evaluated by measuring the magnitude of the respiratory sinus arrhythmia in 3 female patients with hyperthyroidism (Basedow-Graves' disease) before and after treatment. The heart rate variations induced by the test increased in all patients after treatment of thyrotoxicosis (from 15 + or - 2.9 to 28.3 + or - 6.6 beats/min; mean + or - SEM) with propylthiouracil (600 mg/day). This result confirms our previous observations indicating an important and reversible impairment of the efferent vagal activity in human hyperthyroidism

Bradycardic responses to vagal stimulation and methacholine injection in sinoaotic denervated rats

The bradycardia that occurs in response to vagal stimulation or to methacholine after 6 h of sinoaort denervation (SAD) was studied in SAD rats before and agter adrenergic blockade to determinewhether the peripheral vagal action was impaired by sympathetic hyperactivity. A marked attenuation in the response to methacholine and no difference in the responses to vagal stimulation were observed in SAD rats compared to sham-operated controls. The adrenergic blockade attenuated the responses to both vagal stimulation and nethacholine in control rats but not in SAD rats. These finding revealed an impairment of peripheral vagal function after 6 h of SAD, probaly due to a decreased sensitivity of the muscarinic receptors