Particle Effects on Heart-Rate Regulation in Senescent Mice

Because epidemiology studies consistently identify the elderly at risk for air pollution-related morbidity and mortality, we developed a model of senescent-dependent susceptibility based on indices of physiological aging. In the current study, we hypothesized that heart-rate regulation during particulate matter (PM) exposure differs with senescence-dependent susceptibility owing to variation in autonomic nervous control. Heart rate (HR) and heart-rate variability (HRV) parameters were measured from 162 samples of 2-min electrocardiograph (ECG) recordings in age-matched healthy (n = 5) and terminally senescent (n = 3) AKR mice during 3-h exposures to filtered-air (FA, day 1) and carbon black (CB, day 4; < 200 μ g/m³). On day 1, HR was significantly (p <. 01) depressed during FA in terminally senescent mice. By day 4, HR was further slowed significantly (p <. 01) due to the effects of CB exposure for 3 days. The combined effects of terminal senescence and CB exposure acted to depress HR to an average (±SEM) 445 ± 40 bpm, or ～ 80 bpm lower compared to healthy HR responses. The change in rMSSD, an HRV parameter corresponding to relative influences of parasympathetic tone on HR, was significantly (p <. 01) greater on day 1 and day 4 in terminally senescent mice compared to healthy mice. In contrast, the LF/HF ratio, an HRV parameter derived from spectral analysis indicating relative changes in cardiac sympathetic tone, was significantly (p <. 01) depressed in terminally senescent mice on day 1. By day 4, significant increases in LF/HF were evident in healthy mice during CB exposure, suggesting that HR regulation was associated with an increase in sympathetic tone. Alternatively, terminally senescent mice appeared to modulate a lower HR without change in LF/HF ratio during CB exposure, suggesting an absence of sympathetic tone. In conclusion, older healthy mice increase cardiac sympathetic tone during PM exposure while terminally senescent mice show a greater PM-induced parasympathetic tone in regulating HR. The significance of the current results suggest that PM-induced HR regulatory changes may ultimately depend on the degree of physiological aging.     

Variation in heart rate regulation and the effects of particle exposure in inbred mice

Altered autonomic control of heart rate (HR) rhythm during exposure to particulate matter (PM) has been suggested in human and animal studies. Our lab has shown strain variation in HR regulation between quiescent C3H/HeJ (C3) and C57BL/6J (B6) mice: that is, C3 mice show a consistently higher HR by approximately 80 bpm compared with B6 mice during a normal 24-h circadian cycle. In the current study, we hypothesize that the balance between sympathetic and parasympathetic control of HR during PM exposure varies between C3 and B6 mice. Radiotelemeters were implanted in C3 and B6 mice to measure HR responses and HR variability (HRV) parameters during successive 3-h exposures to filtered air (FA) or carbon black (CB, < 300 mug/m3). Exposures were repeated following administration of saline or parasympathetic (PS; atropine, 0.5 mg/kg i.p.) and sympathetic (S; propranolol, 1 mg/kg i.p.) blockade to study the autonomic regulation of HR during CB exposure. During FA exposure with saline, a significantly (p < .05) greater 3-h average HR response (bpm +/- SEM) occurred in C3 compared with B6 mice (496 +/- 22 vs. 427 +/- 3). With PS blockade, the strain difference between C3 and B6 mice was not evident (485 +/- 23 vs. 503 +/- 61). With S blockade, the 3-h average HR responses for C3 mice were significantly (p < .05) reduced compared with saline (413 +/- 18 vs. 392 +/- 15 for B6). During CB exposure with saline, HR responses were again significantly (p < 0.05) elevated in C3 compared with B6 mice, but these HR responses were not different relative to FA exposure. With S blockade, HR was significantly (p < .05) elevated in B6 mice during CB relative to FA, but was unchanged in C3 mice. Collectively, these results suggest that strain variation in HR regulation is due to a robust PS tone evident in B6 mice and a predominant S tone in C3 mice. Furthermore, CB exposure alters HR regulation in B6 mice by modulating a withdrawal of PS tone. Finally, strain variation in HR between B6 and C3 mice in responding to acute PM exposure implies that robust genetic determinants modulate altered autonomic regulation in susceptible individuals.     

Variation in Heart Rate Regulation and the Effects of Particle Exposure in Inbred Mice

Altered autonomic control of heart rate (HR) rhythm during exposure to particulate matter (PM) has been suggested in human and animal studies. Our lab has shown strain variation in HR regulation between quiescent C3H/HeJ (C3) and C57BL/6J (B6) mice: that is, C3 mice show a consistently higher HR by ～ 80 bpm compared with B6 mice during a normal 24-h circadian cycle. In the current study, we hypothesize that the balance between sympathetic and parasympathetic control of HR during PM exposure varies between C3 and B6 mice. Radiotelemeters were implanted in C3 and B6 mice to measure HR responses and HR variability (HRV) parameters during successive 3-h exposures to filtered air (FA) or carbon black (CB, < 300 μg/m³). Exposures were repeated following administration of saline or parasympathetic (PS; atropine, 0.5 mg/kg ip) and sympathetic (S; propranolol, 1 mg/kg ip) blockade to study the autonomic regulation of HR during CB exposure. During FA exposure with saline, a significantly (p < .05) greater 3-h average HR response (bpm ± SEM) occurred in C3 compared with B6 mice (496 ± 22 vs. 427 ± 3). With PS blockade, the strain difference between C3 and B6 mice was not evident (485 ± 23 vs. 503 ± 61). With S blockade, the 3-h average HR responses for C3 mice were significantly (p < .05) reduced compared with saline (413 ± 18 vs. 392 ± 15 for B6). During CB exposure with saline, HR responses were again significantly (p < 0.05) elevated in C3 compared with B6 mice, but these HR responses were not different relative to FA exposure. With S blockade, HR was significantly (p < .05) elevated in B6 mice during CB relative to FA, but was unchanged in C3 mice. Collectively, these results suggest that strain variation in HR regulation is due to a robust PS tone evident in B6 mice and a predominant S tone in C3 mice. Furthermore, CB exposure alters HR regulation in B6 mice by modulating a withdrawal of PS tone. Finally, strain variation in HR between B6 and C3 mice in responding to acute PM exposure implies that robust genetic determinants modulate altered autonomic regulation in susceptible individuals.     

Effects of thiopental and propofol on heart rate variability during fentanyl-based induction of general anesthesia

Anesthetics depress the autonomic nervous system. The effects of thiopental and propofol on heart rate variability (HRV) during fentanyl-based induction of general anesthesia were studied in one hundred patients. We observed different effects of fentanyl, thiopental and propofol on HRV. Fentanyl decreased total power of HRV and low frequency power (LF), but not high frequency power (HF), indicating a greater reduction of cardiac sympathetic activity. Thiopental and propofol caused the further reduction of HRV and decreased HF power. Thiopental increased LF power and LF/HF ratio, indicating that the vagolytic effect is associated with the increase in sympathetic activity. Propofol preserved the LF power, indicating that the cardiac parasympathetic activity is reduced more than the sympathetic activity.     

Heart Rate Variability in Neonatal Rats After Perinatal Cocaine Exposure

Pregnant rats received saline once daily (Control QD) or twice daily (Control BID), cocaine 2 mg/kg IV daily (COC QD) or twice daily (COC BID) throughout gestation beginning on gestational day 4. The treatment was continued in nursing mothers until postnatal day 7. All studies were performed in their offsprings on postnatal days 1 and 7. An age-dependent increase in heart rate was observed from D1 to D7 in all four groups of animals. Cocaine exposure significantly increased heart rate in the once daily treatment group on D1 and D7. In contrast, twice daily cocaine exposure did not alter heart rate. Maturational changes in heart rate variability (HRV) were also documented. Low-frequency (LF: 0.25–0.8 Hz) power of HRV is a marker of both sympathetic and parasympathetic influences, and high-frequency (HF: 0.8–2.4 Hz) power is a marker of efferent vagal activity. Total power (TP) is the sum of LF and HF. TP, normalized units of LF (LF as percent of TP), and normalized HF power decreased from D1 to D7 in all groups. Cocaine treatment affected both LF and HF powers and there was an interaction between cocaine treatment and age for both LF and HF. Although LF/HF ratio decreased from D1 to D7 in both groups of control animals, LF/HF did not change from D1 to D7 in either cocaine-treated group. Thus, cocaine exposure significantly attenuated the age-dependent change in LF/HF. Our results indicated that there were normal developmental changes in HRV consistent with continued postnatal development of autonomic nervous system. Perinatal cocaine exposure appeared to modify these changes. The specific autonomic mechanism for the cocaine effect may be a decline in parasympathetic activity and a concomitant change in sympathetic activity.     

Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. IV. Characterization of acute and chronic effects of ambient air fine particulate matter exposures on heart-rate variability

Long-term exposure to fine particulate air pollution (PM2.5) has been associated increased risk of death from cardiopulmonary diseases. Cardiac function parameters have also been affected by ambient particulate matter (PM) exposure, including heart-rate variability (HRV), a measure of autonomic function that has been recognized as a well-defined, quantitative indicator of autonomic dysfunction. However, the role of HRV in ambient PM-induced cardiovascular effect is not fully understood. In an accompanying article, we report significant decreasing patterns of heart rate (HR), body temperature, and physical activity for mice lacking apoliproprotein (ApoE-/-) over 5 mo of exposure to concentrated ambient PM (CAPs), with smaller and nonsignificant change for C57 mice. In this article, we report the effects of subchronic CAPs exposure on HRV parameters that are sensitive to cardiac sympathetic and parasympathetic nerve activity. The standard deviation of normal to normal beat intervals (SDNN) and the square root of the mean squared differences of successive RR intervals (RMSSD) in the late afternoon and overnight for the ApoE-/- mice showed a gradual increase for the first 6 wk, a decline for about 12 more wk, and a slight turn upward at the end of the study period. For C57 mice, there were no chronic effect changes of SDNN or RMSSD in the late afternoon, an a slight increase after 6 wk for the overnight period. The response patterns of ApoE-/- mice indicated a perturbation of the homeostatic function in the cardiovascular system (initial enhancement and late depression of the HRV parameters). Our results complement the findings in human panel and controlled CAPs exposure studies in demonstrating that increased levels of particle pollution are able to perturb cardiac autonomic function, which may lead to adverse cardiovascular outcomes.     

Effects of sirsasana (headstand) practice on autonomic and respiratory variables.

The present study had two aims: (1) To assess heart rate variability (HRV) along with non-specific autonomic measures (used in earlier studies), before and after two minutes of the head stand. (2) To compare changes in two categories of subjects, i.e., those who practiced the headstand in a traditional way (without any support) and those who used the support of the wall (a present day adaptation). The subjects were forty male volunteers (age range 19 to 36 years), with twenty subjects under each category. The following changes were significant after the practice, compared to values at baseline. (i) Both categories had an increase in the power of the low frequency component (LF) and a decrease in the high frequency component (HF) of the HRV spectrum, increased LF/HF ratio, and decreased heart rate. (ii) Subjects who practiced the head stand with the support of a wall showed reduced finger plethysmogram amplitude suggesting increased sympathetic vasomotor tone. (iii) Practicing the headstand without support was associated with an increase in the skin conductance level, suggestive of increased sympathetic sudomotor tone. Hence, both categories showed similar changes in the HRV components though changes in sympathetic vasomotor and sudomotor activity were different. These changes suggest sympathetic activation, irrespective of the method of practice.     

心率变异性的频谱分析

采用频谱法对比分析正常人，急性心肌梗塞和心力衰竭病人昼夜不同时间的心率变异性。结果发现正常人白天低频成份占优势，夜间高频成份相对增加，４０岁以上及６０以上两年龄组的两种频率成份显著低于４０岁以下组，心肌梗塞和心力衰竭病人两种频段的功率密度均下降，且昼夜的生理性波动减小，结论认为频谱分析能反映交感神经与迷走神经活性的高低和平衡。     

Effects of Subchronic Exposures to Concentrated Ambient Particles (CAPs) in Mice: IV. Characterization of Acute and Chronic Effects of Ambient Air Fine Particulate Matter Exposures on Heart-Rate Variability

Abstract

Long-term exposure to fine particulate air pollution (PM_2.5) has been associated with increased risk of death from cardiopulmonary diseases. Cardiac function parameters have also been affected by ambient particulate matter (PM) exposure, including heart-rate variability (HRV), a measure of autonomic function that has been recognized as a well-defined, quantitative indicator of autonomic dysfunction. However, the role of HRV in ambient PM-induced cardiovascular effects is not fully understood. In an accompanying article, we report significant decreasing patterns of heart rate (HR), body temperature, and physical activity for mice lacking apoliproprotein (ApoE^?/?) over 5 mo of exposure to concentrated ambient PM (CAPs), with smaller and nonsignificant changes for C57 mice. In this article, we report the effects of subchronic CAPs exposure on HRV parameters that are sensitive to cardiac sympathetic and parasympathetic nerve activity. The standard deviation of normal to normal beat intervals (SDNN) and the square root of the mean squared differences of successive RR intervals (RMSSD) in the late afternoon and overnight for the ApoE^?/? mice showed a gradual increase for the first 6 wk, a decline for about 12 more wk, and a slight turn upward at the end of the study period. For C57 mice, there were no chronic effect changes of SDNN or RMSSD in the late afternoon, and a slight increase after 6 wk for the overnight period. The response patterns of ApoE^?/? mice indicated a perturbation of the homeostatic function in the cardiovascular system (initial enhancement and later depression of the HRV parameters). Our results complement the findings in human panel and controlled CAPs exposure studies in demonstrating that increased levels of particle pollution are able to perturb cardiac autonomic function, which may lead to adverse cardiovascular outcomes.     

心理应激对心率变异影响的研究

目的观察应用小剂量倍他乐克对部队战士心理应激心率变异的影响,评价小剂量倍他乐克对心理应激心血管自主神经的调节作用。方法被试者为800名部队新、老战士,年龄18～22岁,均衡分为betaloc组(服用倍他乐克6.25mg/次,2次/d,共1周),对照组(服用安慰剂)。服药前和应急训练前应用SCL-90症状自评量表测评,采用Holter记录服药前30min及应急训练前30min的心电信号,进行心率变异(HRV)分析。结果新、老战士在应急训练前SCL-90症状自评量表总分和阳性项目数显著升高,LF均升高,HF下降,LF/HF升高,有显著性差异,且二者有相关性。对照组较betaloc组LF升高更显著穴P<0.05雪,服用倍他乐克使心理应激时HF降低幅度显著减少。结论心理应激使心脏交感神经兴奋、迷走神经抑制,心率变异性降低,小剂量倍他乐克可提高心理应激时的心率变异性,使心脏交感神经和迷走神经的平衡调节改善。     

哮喘儿童血浆神经肽Y与心率变异性相关性分析

目的 探讨哮喘儿童血浆神经肽Y（NPY）含量与其心率变异性（HRV）的关系。方法 随机选择哮喘儿童35例与健康儿童40例测定其空腹血浆NPY浓度，同时做24h动态心电图并进行HRV时域分析。结果 HRV中反映迷走神经张力指标的高频（HF）、rMSSD和pNN50在哮喘儿童组数值明显高于正常对照组（P〈0．01），而反映交感神经张力的主要指标低频（LF）、SDNN和SDANN则明显低于对照组。哮喘儿童血浆NPY明显升高（P〈0．01），NPY与rMSSD（r=0．76）、pNN50（r=0．71）呈正相关。结论 哮喘儿童血浆NPY与其HRV密切相关。     

Effect of autonomic nervous function on QT interval in dogs

The effects of drugs on the QT interval should be evaluated precisely in the early stages of drug development because QT prolongation can trigger the so-called torsades de pointes, a life-threatening polymorphic ventricular tachycardia. It has been reported that the QT interval is affected by autonomic nervous tone besides the heart rate. In this study, we investigated the direct effect of autonomic nervous tone on the QT interval using the parameters of heart rate variability in dogs, when the RR interval was constant (400 or 700 msec). Our results showed that the QT interval at the high HF (high vagal tone) or low LF/HF ratio (low sympathetic tone) was longer than that at the low HF (low vagal tone) or high LF/HF ratio (high sympathetic tone), when the RR intervals were constant, and that the effect of vagal tone on the QT interval might be somewhat stronger than that of the sympathetic tone. The present observations would support the idea that sympathetic as well as parasympathetic tone regulates QT interval and that QT interval may be controlled physiologically by myocardial autonomic nerves via and not via a sinus node. Therefore, a more precise correction formula of QT interval could be established using autonomic parameters other than RR interval (heart rate), while the QT interval is widely known to be dependent on the RR interval or heart rate.     

阿托伐他汀对心肌梗死患者心率变异性的影响

目的:观察阿托伐他汀对急性心肌梗死(AMI)患者和陈旧性心肌梗死(OMI)患者心率变异性(HRV)的影响。方法:AMI和OMI患者各48例均随机分为试验组和对照组,每组各24例,试验组在常规治疗基础上加用阿托伐他汀10～20 mg·d-1,qd,疗程4周。对照组仅采用常规治疗(酒石酸美托洛尔12．5～50 mg,bid,硝酸异山梨酯5～10 mg,tid)。治疗前后用数字化24 h Holter记录测定心率变异性时域参数(SDNN)和频域参数(LF和HF)。结果:AMI患者试验组治疗4周后,HRV各项指标均明显好转,SDNN,LF和HF均明显增加,LF／HF明显降低,与治疗前比较和组间比较差异均有显著性(P<0．05)。OMI患者试验组SDNN与治疗前比较及组间比较无明显变化(P>0．05),LF和HF均明显增加,LF／HF明显降低,与治疗前比较和组间比较差异有显著性(P<0．05)。结论:阿托伐他汀具有降低心肌梗死患者交感神经活性,提高迷走神经张力的作用,使LF／HF趋于正常,提示该药具有稳定AMI患者自主神经功能的作用。     

脑卒中患者心率变异性特征研究

目的 观察脑卒中与非脑卒中患者的心率变异性(heart rate variability,HRV),探讨脑卒中对HRV的影响.方法 选择2012年7月—2013年9月收治的72例脑卒中作为观察组,选择同期住院的非脑血管疾病患者80例作为对照组.对两组进行24 h的HRV监测,于入院后24 h和治疗1个月后分别进行监测,观察两组HRV的变化情况.结果 观察组在入院后24 h和治疗1个月后全程全部窦性R-R间期的标准差(SDNN)、24 h内每5分钟时段窦性R-R间期平均值的标准差(SDANN)、全程全部窦性R-R间期的平方根(rMSSD)、两个相邻R-R间期互差>50 ms的心跳次数所占分析信息间期内心搏数的百分比(PNN50)、总功率谱(TP)、低频功率谱(LF)、高频功率谱(HF)较对照组降低,LF/HF较对照组增高(P<0.05);观察组治疗1个月后SDNN、SDANN、rMSSD、PNN50、TP、LF、HF较入院后24 h升高,LF/HF较入院24 h降低(P<0.05).观察组入院24 h日间和夜间HRV比较差异无统计学意义(P>0.05);观察组治疗1个月和对照组夜间HRV均高于日间(P<0.05);观察组治疗1个月后日间和夜间SDNN、SDANN、rMSSD、PNN50、夜间LF、夜间HF并较入院24h时均显著升高,LF/HF、TP、日间LF、日间HF较入院24 h时降低(P<0.05).结论 脑卒中患者HRV昼夜间波动节律减弱或消失,植物神经功能受损严重,随着治疗时间的延长,迷走和交感神经间逐渐平衡调控,HRV节律逐步恢复.     

脑出血患者心率变异性分析

目的:探讨脑出血患者的心率变异性,从而了解脑出血对植物神经功能的影响。方法:采用时域和频域两种方法对34例脑出血患者与38例高血压和30例正常人的心率变异作对比分析。结果:脑出血患者的SDNN、SDANN、SDANNI、TF、LF、LF/HF比值明显低于高血压组和正常对照组,有显著性差异(P<0.05或P<0.01)。结论:脑出血急性期心率变异明显降低,以交感神经功能降低更显著,交感和迷走神经功能失调。     

Heart rate variability in normotensive subjects with family history of hypertension

Hypertension (HT) is a major silent disease affecting young people because of their hereditary and modern lifestyles. Target organ damages occur before overt hypertension is diagnosed. Many offspring of HT parents show early changes in their cardiovascular autonomic functions. Heart rate variability (HRV) provides a window to understand the cardiac autonomic balance. This study was designed to quantify and to compare the HRV among the normotensive young male offspring without history of parenteral hypertension & diabetic (control group, n = 25, age 20.8 +/- 2.4, BMI 24.4 +/- 3.1) with parenteral history of hypertension & non diabetic (study group n = 25, age 19.7 +/- 1.9, 24.05 +/- 3.5). Blood pressure, heart rate (HR), indices of short term HRV during supine rest and quiet standing, HR variation during timed controlled deep breathing was compared between the two groups. There were significant difference in low frequency (LF) power, HF power, total power. LF and HF expressed also in normalized units at rest and standing. In time domain standard deviation of normal to normal RR interval (SDNN) at supine rest and standing were significant. Respiratory sinus arrthymia (RSA), HF in normalized units, deep breathing difference (BDD) and the ratio of maximum RR to minimum RR were also significant in the control group than study group. In the present study there was an increased sympathetic and decreased parasympathetic activity in the study group. These findings are an early marker of cardiovascular autonomic impairment in subjects with parenteral history of hypertension.     

Autonomic nervous system activity imbalance in cardiomyopathic hamster

There is strong evidence that autonomic imbalance plays an important role in progression of heart failure. Analysis of heart rate variability (HRV) has achieved substantial acceptance as a noninvasive method for the assessment of autonomic tone. The purpose of this investigation was to study HRV in an experimental model of heart failure using cardiomyopathic (BIO TO.2) hamsters. Animals showed an autonomic imbalance of cardiac control that seems due to attenuation of parasympathetic activity and an enhanced sympathetic tone. The reduction of parasympathetic activity in BIO TO.2 hamsters is suggested by (a) the reduction of the high-frequency (HF) spectrum, and (b) the lack of atropine to generate a response. The increased sympathetic activity is indicated by (a) the decreased time-domain indexes, (b) the increased LF/HF ratio of the power spectrum, and (c) the alteration of HRV indexes induced by propranolol. These results support the notion that in heart failure, there is a similar autonomic imbalance in both human and hamster and suggest that the cardiomyopathic hamster is a suitable experimental model for studying the involvement of the autonomic nervous system in the progression of heart failure.     

Comparison between pre-prandial and post-prandial heart rate variability (HRV)

After food ingestion, peptides are released in GIT, which cause local vasodilatation. Therefore, after meals, redistribution of blood occurs because of shifting of large amounts of blood into GIT. In normal individuals, this is well compensated and does not lead to post-prandial hypotension. The mechanism of post-prandial hypotension is well known. We hypothesized that there may be a decrease in parasympathetic activity (tone) after meals to compensate for the change in blood distribution. We carried out the study to find out the changes in the autonomic tone before and after meals (lunch) in normal individuals, using Heart Rate Variability (HRV). From the series of RR intervals marked, the time domain and frequency domain measures of HRV were obtained using Nevrokard software (version 6.4). Continuous ECG was recorded in 15 healthy adult subjects (mean age 29.06 +/- 6.2; 13 males and 2 females). The ECG was recorded in pre-prandial and post-prandial state for a period of five minutes each as follows: (1) just before the subjects had lunch, (2) 15 minutes after lunch, (3) 1 hour after lunch, and (4) 2 hours after lunch. Time domain and frequency domain measures of HRV were compared between pre-prandial state and rest of post-prandial states. The autonomic tone parameters did not show a significant change between the pre-prandial state and the immediate post-prandial state. [Range, i.e., the difference between the maximum and minimum RR intervals (406 +/- 161.14 vs. 416.66 +/- 125), standard-deviation of normal to normal RR interval (56.33 +/- 22.72 vs. 67.63 +/- 26.50), RMSSD (55.02 +/- 35.85 vs. 63.87 +/- 32.60), NN50 (42.13 +/- 29.43 vs. 51.86 +/- 29.83), PNN50 (12.67 +/- 10.29 vs. 15.27 +/- 9.71), HF (49.53 +/- 15.10 vs. 47.07 +/- 16.88), LF (41.41 +/- 13.18 vs. 46.49 +/- 15.99), LF/HF (0.98 +/- 0.53 vs. 1.26 +/- 0.90), total power (148.27 +/- 37.78 vs. 137.61 +/- 37.10)]. No significant change was seen in the above parameters between the pre-prandial state and the later phases of post-prandial state. Since there is no significant decrease in the time domain measures and the HF value between the pre-prandial and the post-prandial states, we conclude that the parasympathetic tone is not altered. The parameters denoting sympathetic tone, ie, LF and LF/HF, also do not show a significant change. This indicates that the cardiovascular autonomic tone is not affected by ingestion of meals in normal individuals. Thus we refute our hypothesis. In conclusion, the HRV parameters do not alter significantly after meals in normal individuals.     

Intermittent clonidine regimen abolishes tolerance to its antihypertensive effect: a spectral study

The development of tolerance to the antihypertensive effect of clonidine and related imidazolines is clinically recognized. Here, we employed a restricted daytime (8:30 AM until 4:30 PM) clonidine regimen to establish a model of sustained hypotension in spontaneously hypertensive rats (SHRs). Blood pressure (BP), heart rate (HR), and myocardial contractility (dP/dt(max)) were measured by radiotelemetry in pair-fed SHRs receiving liquid diets with or without clonidine (150 microg/kg per day) for 12 weeks. The cardiovascular autonomic control was assessed by power spectral analysis [fast Fourier transformations (FFT)] of hemodynamic variability. Clonidine had no effect on dP/dt(max) and significantly decreased BP and HR during the 8 hour exposure periods throughout the study duration. BP returned to control levels during overnight periods, with no signs of rebound hypertension. FFT analysis of interbeat intervals (IBI) showed pronounced decreases and increases of spectral powers in low-frequency (IBI-LF, 0.20-0.75 Hz) and high-frequency (IBI-HF, 0.75-3 Hz) bands, respectively, in clonidine-treated rats. The IBI(LF/HF) ratio was significantly reduced by clonidine, suggesting cardiac parasympathetic dominance. Clonidine also decreased the vasomotor sympathetic tone, as reflected by the reduced BP-LF spectral density. The sympathoinhibitory effect of clonidine is further confirmed by the significant reductions in urinary norepinephrine levels. Clonidine increased urine output during the 8 hour treatment period but not during the 24 hour period. Plasma and urine osmolality and electrolytes were not altered by clonidine. It is concluded that by adopting the limited-access paradigm, tolerance to the hypotensive and sympathoinhibitory actions of clonidine and, possibly, its side effects, could be minimized.     

Nitric oxide modulates cardiovascular function in the rat by activating adenosine A2A receptors and inhibiting acetylcholine release in the rostral ventrolateral medulla

1. Nitric oxide (NO), a gas transmitter, modulates many physiological processes, including the central regulation of cardiovascular activity. However, the mechanisms underlying the regulation of cardiovascular activity remain relatively unexplored. In the present study, we hypothesized that central NO-dependent sympathetic inhibition is mediated by activation of adenosine A(2A) receptors (A(2A)R) and inhibition of acetylcholine (ACh) release in the rostral ventrolateral medulla (RVLM). 2. L-Arginine (L-Arg; an NO donor; 100 nmol/100 nL) was microinjected into the RVLM of male Sprague-Dawley rats and heart rate variability (HRV) was assessed as an index of cardiac sympathovagal balance. Following microinjection of L-Arg, decreases were seen in mean arterial pressure (MAP), heart rate (HR) and the ratio of the low- to high-frequency components (LF/HF) of HRV. Pretreatment of rats with SCH58261 (40 pmol/60 nL into the RVLM), a competitive antagonist of the A(2A) R, attenuated these effects. 3. Western blot analysis and ELISA revealed that adenosine and A(2A)R levels increased in the RVLM following L-Arg microinjection, whereas ACh and muscarinic M(1) receptor levels decreased significantly, in parallel with the cardiovascular responses to L-Arg microinjection. The decrease in ACh levels was abolished by SCH58261 pretreatment. 4. Microinjection of N(G)-nitro-L-arginine methyl ester (a non-selective inhibitor of NO synthase; 15 nmol/100 nL) into the RVLM significantly increased MAP, HR and sympathetic activity, as evidenced by HRV (LF, HF and the LF/HF ratio were all increased). 5. The results indicate that the central NO/NO synthase system in the RVLM may modulate cardiovascular activity by activating the A(2A)R, which subsequently inhibits activation of the muscarinic M(1) receptor.