Circadian changes in the sensitivity of the baroreflex in the conscious rat

The cardiac baroreflex sensitivity (BRS) was measured in quiet awake rats after phenylephrine injections. It was shown that BRS progressively increased during daytime (rest period) and decreased at the beginning of the night (activity period). These variations were independent from the levels of blood pressure and heart period recorded before the BRS measurements.     

Hemodynamic and autonomic correlates of postexercise hypotension in patients with mild hypertension

We investigated the interplay of neural and hemodynamic mechanisms in postexercise hypotension (PEH) in hypertension. In 15 middle-aged patients with mild essential hypertension, we evaluated blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR), forearm (FVR) and calf vascular resistance (CVR), and autonomic function [by spectral analysis of R-R interval and BP variabilities and spontaneous baroreflex sensitivity (BRS)] before and after maximal exercise. Systolic and diastolic BP, TPR, and CVR were significantly reduced from baseline 60-90 min after exercise. CO, FVR, and HR were unchanged. The low-frequency (LF) component of BP variability increased significantly after exercise, whereas the LF component of R-R interval variability was unchanged. The overall change in BRS was not significant after exercise vs. baseline, although a significant, albeit small, BRS increase occurred in response to hypotensive stimuli. These findings indicate that in hypertensive patients, PEH is mediated mainly by a peripheral vasodilation, which may involve metabolic factors linked to postexercise hyperemia in the active limbs. The vasodilator effect appears to override a concomitant, reflex sympathetic activation selectively directed to the vasculature, possibly aimed to counter excessive BP decreases. The cardiac component of arterial baroreflex is reset during PEH, although the baroreflex mechanisms controlling heart period appear to retain the potential for greater opposition to hypotensive stimuli.     

A transfer function method for the continuous assessment of baroreflex control of renal sympathetic nerve activity in rats

The present study examined whether the gain of the transfer function relating cardiac-related rhythm of renal sympathetic nerve activity (RSNA) to arterial pressure (AP) pulse might serve as a spontaneous index of sympathetic baroreflex sensitivity (BRS). AP and RSNA were simultaneously recorded in conscious rats, either baroreceptor-intact (control, n = 11) or with partial denervation of baroreflex afferents [aortic baroreceptor denervated (ABD; n = 10)] during 1-h periods of spontaneous activity. Transfer gain was calculated over 58 adjacent 61.4-s periods (segmented into 10.2-s periods). Coherence between AP and RSNA was statistically (P < 0.05) significant in 90 +/- 3% and 56 +/- 10% of cases in control and ABD rats, respectively. Transfer gain was higher (P = 0.0049) in control [2.39 +/- 0.13 normalized units (NU)/mmHg] than in ABD (1.48 +/- 0.22 NU/mmHg) rats. In the pooled study sample, transfer gain correlated with sympathetic BRS estimated by the vasoactive drug injection technique (R = 0.75; P < 0.0001) and was inversely related to both time- (standard deviation; R = -0.74; P = 0.0001) and frequency-domain [total spectral power (0.00028-2.5 Hz); R = -0.82; P < 0.0001] indices of AP variability. In control rats, transfer gain exhibited large fluctuations (coefficient of variation: 34 +/- 3%) that were not consistently related to changes in the mean level of AP, heart rate, or RSNA. In conclusion, the transfer function method provides a continuous, functionally relevant index of sympathetic BRS and reveals that the latter fluctuates widely over time.     

Relating drug-induced changes in carotid artery mechanics to cardiovagal and sympathetic baroreflex control

Previous evidence indicates that sensitivity of the baroreflex cardiovagal and sympathetic arms is dissociated. In addition, pharmacologic assessment of baroreflex sensitivity (BRS) has revealed that cardiovagal, but not sympathetic, BRS is greater when blood pressure is increasing versus falling. The origin of this hysteresis is unknown. In this study, carotid artery distensibility and absolute distension (diameter) were assessed to test the hypothesis that vessel mechanics in barosensitive regions affect the BRS of cardiovagal, but not sympathetic, outflow. R-R interval (i.e. time between successive R waves), finger arterial blood pressure, muscle sympathetic nerve activity, and carotid artery dimensions (B-mode imaging) were measured during sequential infusions of sodium nitroprusside (SNP) and phenylephrine (PHE). Systolic and diastolic common carotid artery diameters and pulse pressure were recorded to calculate distensibility of this vessel under each drug condition. Cardiovagal BRS was greater when blood pressure was increasing versus decreasing (p < 0.01). Sympathetic BRS was not affected by direction of pressure change. Distensibility did not differ between SNP and PHE injections. However, compared with SNP, infusion of PHE resulted in larger absolute systolic and diastolic carotid diameters (p < 0.001). Therefore, cardiovagal reflex hysteresis was related to drug-induced changes in common carotid artery diameter but not distensibility. The lack of sympathetic hysteresis in this model suggests a relative insensitivity of this baroreflex component to carotid artery dimensions and provides a possible mechanism for the dissociation between cardiovagal and sympathetic BRS.     

Aldosterone impairs baroreflex sensitivity in healthy adults

Animal studies suggest that acute and chronic aldosterone administration impairs baroreceptor/baroreflex responses. We tested the hypothesis that aldosterone impairs baroreflex control of cardiac period [cardiovagal baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA, sympathetic BRS) in humans. Twenty-six young (25 +/- 1 yr old, mean +/- SE) adults were examined in this study. BRS was determined by using the modified Oxford technique (bolus infusion of nitroprusside, followed 60 s later by bolus infusion of phenylephrine) in triplicate before (Pre) and 30-min after (Post) beginning aldosterone (experimental, 12 pmol.kg(-1).min(-1); n = 10 subjects) or saline infusion (control; n = 10). BRS was quantified from the R-R interval-systolic blood pressure (BP) (cardiovagal BRS) and MSNA-diastolic BP (sympathetic BRS) relations. Aldosterone infusion increased serum aldosterone levels approximately fourfold (P < 0.05) and decreased (P < 0.05) cardiovagal (19.0 +/- 2.3 vs. 15.6 +/- 1.7 ms/mmHg Pre and Post, respectively) and sympathetic BRS [-4.4 +/- 0.4 vs. -3.0 +/- 0.4 arbitrary units (AU).beat(-1).mmHg(-1)]. In contrast, neither cardiovagal (19.3 +/- 3.3 vs. 20.2 +/- 3.3 ms/mmHg) nor sympathetic BRS (-3.8 +/- 0.5 vs. -3.6 +/- 0.5 AU.beat(-1).mmHg(-1)) were altered (Pre vs. Post) in the control group. BP, heart rate, and MSNA at rest were similar in experimental and control subjects before and after the intervention. Additionally, neural and cardiovascular responses to a cold pressor test and isometric handgrip to fatigue were unaffected by aldosterone infusion (n = 6 subjects). These data provide direct experimental support for the concept that aldosterone impairs baroreflex function (cardiovagal and sympathetic BRS) in humans. Therefore, aldosterone may be an important determinant/modulator of baroreflex function in humans.     

Modification of Baroreceptor Cardiac Reflex Function by Biofeedback

Baroreceptor sensitivity (BRS) is considered a powerful prognostic factor in cardiovascular health. This study investigated the possibility of modifying the baroreflex cardiac function through biofeedback. Thirty-two psychology students underwent 3 biofeedback sessions, with four 5-min trials each, in which they had to increase and decrease baroreflex function. BRS was assessed by a system that analyzed baroreflex cardiac function on-line using a noninvasive spontaneous sequence method in the time domain. Baroreceptor parameters were differentiated in terms of blood pressure increases ("up" sequences) or blood pressure decreases ("down" sequences). BRS in the "up" sequences increased during the Increase Condition and decreased during the Decrease Condition. BRS in the "down" sequences decreased during the Decrease Condition but was unchanged during the Increase Condition. The increase in BRS during the Increase Condition was associated with a significant reduction in blood pressure and increase in heart period. The opposite cardiovascular changes were observed during the Decrease Condition. Suggestions for future research were discussed.     

Cyclosporine attenuates the autonomic modulation of reflex chronotropic responses in conscious rats

Cyclosporine A (CyA), an immunosuppressant drug, has been shown to attenuate the baroreflex control of heart rate (HR). This study investigated whether or not the CyA-induced baroreflex dysfunction is due to alterations in the autonomic (sympathetic and parasympathetic) control of the heart. We evaluated the effect of muscarinic or beta-adrenergic blockade by atropine and propranolol, respectively, on reflex HR responses in conscious rats treated with CyA (20 mg x kg(-1) x day(-1) dissolved in sesame oil) for 11-13 days or the vehicle. Baroreflex curves relating changes in HR to increases or decreases in blood pressure (BP) evoked by phenylephrine (PE) and sodium nitroprusside (NP), respectively, were constructed and the slopes of the curves were taken as a measure of baroreflex sensitivity (BRS(PE) and BRS(NP)). Intravenous administration of PE and NP produced dose-related increases and decreases in BP, respectively, that were associated with reciprocal changes in HR. CyA caused significant (P < 0.05) reductions in reflex HR responses as indicated by the smaller BRS(PE) (-0.97 +/- 0.07 versus -1.47 +/- 0.10 beats x min(-1) x mmHg(-1) (1 mmHg = 133.322 Pa)) and BRS(NP) (-2.49 +/- 0.29 versus -5.23 +/- 0.42 beats x min(-1) x mmHg(-1)) in CyA-treated versus control rats. Vagal withdrawal evoked by muscarinic blockade elicited significantly lesser attenuation of BRS(PE) in CyA compared with control rats (40.2 +/- 8.0 versus 57.7 +/- 4.4%) and abolished the BRS(PE) difference between the two groups, suggesting that CyA reduces vagal activity. CyA also appears to impair cardiac sympathetic control because blockade of beta-adrenergic receptors by propranolol was less effective in reducing reflex tachycardic responses in CyA compared with control rats (41.6 +/- 4.2 versus 59.5 +/- 4.5%). These findings confirm earlier reports that CyA attenuates the baroreceptor control of HR. More importantly, the study provides the first pharmacological evidence that CyA attenuates reflex chronotropic responses via impairment of the autonomic modulation of the baroreceptor neural pathways.     

Baroreflex control of lumbar and renal sympathetic nerve activity in conscious rats

This study compared the baroreflex control of lumbar and renal sympathetic nerve activity (SNA) in conscious rats. Arterial pressure (AP) and lumbar and renal SNA were simultaneously recorded in six freely behaving rats. Pharmacological estimates of lumbar and renal sympathetic baroreflex sensitivity (BRS) were obtained by means of the sequential intravenous administration of sodium nitroprusside and phenylephrine. Sympathetic BRS was significantly (P < 0.05) lower for lumbar [3.0 +/- 0.4 normalized units (NU)/mmHg] than for renal (7.6 +/- 0.6 NU/mmHg) SNA. During a 219-min baseline period, spontaneous lumbar and renal BRS were continuously assessed by computing the gain of the transfer function relating AP and SNA at heart rate frequency over consecutive 61.4-s periods. The transfer gain was considered only when coherence between AP and SNA significantly differed from zero, which was verified in 99 +/- 1 and 96 +/- 3% of cases for lumbar and renal SNA, respectively. When averaged over the entire baseline period, spontaneous BRS was significantly (P < 0.05) lower for lumbar (1.3 +/- 0.2 NU/mmHg) than for renal (2.3 +/- 0.3 NU/mmHg) SNA. For both SNAs, spontaneous BRS showed marked fluctuations (variation coefficients were 26 +/- 2 and 28 +/- 2% for lumbar and renal SNA, respectively). These fluctuations were positively correlated in five of six rats (R = 0.44 +/- 0.06; n = 204 +/- 8; P < 0.0001). We conclude that in conscious rats, the baroreflex control of lumbar and renal SNA shows quantitative differences but is modulated in a mostly coordinated way.     

"Regulation of the intracerebroventricular administration of brain-derived neurotrophic factor on baroreflex function and insulin sensitivity in rats"

"In addition to its well-established neurotrophic effects, brain-derived neurotrophic factor (BDNF) has also been shown to regulate glucose metabolism. The present study was conducted to determine whether BDNF has effects on baroreflex sensitivity (BRS) and whole-body insulin sensitivity through modulation of autonomic nervous function in normal rats. Male Sprague-Dawley rats were treated with intracerebroventricular BDNF (20 μg per rat, 10μl; BDNF) or artificial cerebrospinal fluid (10 μl; control) at an infusion rate of 1 μl/min in conscious state. The whole-body insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp technique. BRS in response to phenylephrine (PE-BRS) or sodium nitroprusside (NP-BRS) was assessed using linear regression analysis. The sympathetic and parasympathetic influences on BRS were investigated by pharmacological autonomic blockade. When compared to the control rats, blood glucose levels were slightly but significantly decreased in BDNF-treated rats. However, plasma insulin levels were reduced by about 30%. The whole-body insulin sensitivity was increased in BDNF-treated rats. In addition, blood pressure was increased but heart rate remained unchanged after BDNF treatment. Enhanced PE-BRS was also observed in the BDNF-treated rats, which was attributed to the abnormal parasympathetic activation as revealed by the results of the pharmacological blockade study with methylatropine. Results of the present demonstrate that central BDNF plays an important role in the regulation of whole-body insulin sensitivity and baroreflex function. The data indicate that the alteration of autonomic nervous function may play a role in the effects of BDNF."     

Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis

The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P < 0.05). The evoked BRS to increases, but not decreases, in pressure was lower in hydronephrotic rats (1.06 ± 0.06 normal vs. 0.72 ± 0.10 mild/moderate vs. 0.63 ± 0.07 ms/mmHg severe; P < 0.05). Spectral analysis methods confirmed reduced parasympathetic function in hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II.     

Impaired cardiac and sympathetic autonomic control in rats differing in acetylcholine receptor sensitivity

Acetylcholine receptors (AChR) are important in premotor and efferent control of autonomic function; however, the extent to which cardiovascular function is affected by genetic variations in AChR sensitivity is unknown. We assessed heart rate variability (HRV) and baroreflex sensitivity (BRS) in rats bred for resistance (FRL) or sensitivity (FSL) to cholinergic agents compared with Sprague-Dawley rats (SD), confirmed by using hypothermic responses evoked by the muscarinic agonist oxotremorine (0.2 mg/kg i.p.) (n > or = 9 rats/group). Arterial pressure, ECG, and splanchnic sympathetic (SNA) and phrenic (PNA) nerve activities were acquired under anesthesia (urethane 1.3 g/kg i.p.). HRV was assessed in time and frequency domains from short-term R-R interval data, and spontaneous heart rate BRS was obtained by using a sequence method at rest and after administration of atropine methylnitrate (mATR, 2 mg/kg i.v.). Heart rate and SNA baroreflex gains were assessed by using conventional pharmacological methods. FRL and FSL were normotensive but displayed elevated heart rates, reduced HRV and HF power, and spontaneous BRS compared with SD. mATR had no effect on these parameters in FRL or FSL, indicating reduced cardiovagal tone. FSL exhibited reduced PNA frequency, longer baroreflex latency, and reduced baroreflex gain of heart rate and SNA compared with FRL and SD, indicating in FSL dual impairment of cardiac and circulatory baroreflexes. These findings show that AChR resistance results in reduced cardiac muscarinic receptor function leading to cardiovagal insufficiency. In contrast, AChR sensitivity results in autonomic and respiratory abnormalities arising from alterations in central muscarinic and or other neurotransmitter receptors.     

Sildenafil acts on the central nervous system increasing sympathetic activity.

Sildenafil induces vasodilation and is used for treating erectile dysfunction. Although its influence on resting heart function appears to be minimal, recent studies suggest that sildenafil can increase sympathetic activity. We therefore tested whether sildenafil injected into the central nervous system alters the autonomic control of the cardiovascular system in conscious rats. The effect of sildenafil citrate injected into the lateral cerebral ventricle was evaluated in conscious rats by means of the recording of lumbar sympathetic nerve activity (LSNA), spectral analysis of systolic arterial pressure and heart rate variability, spontaneous baroreflex sensitivity, and baroreflex control of LSNA. Intracerebroventricular (ICV, 100 microg /5 microl) administration of sildenafil caused remarkable tachycardia without significant change in basal arterial pressure and was associated with a conspicuous increase (47 +/- 14%) in LSNA. Spectral analysis demonstrated that systolic arterial pressure oscillations in the low frequency (LF) range were increased (from 6.3 +/- 1.5 to 12.8 +/- 3.8 mmHg(2)), whereas the high frequency (HF) range was not affected by ICV administration of sildenafil. Sildenafil increased pulse interval oscillations at LF and decreased them at HF. The LF-HF ratio increased from 0.04 +/- 0.01 to 0.17 +/- 0.06. Spontaneous baroreflex sensitivity measured by the sequence method and the baroreflex relationship between mean arterial pressure and LSNA were not affected by ICV administration of sildenafil. In conclusion, sildenafil elicited an increase in sympathetic nerve activity that is not baroreflex mediated, suggesting that this drug is able to elicit an autonomic imbalance of central origin. This finding may have implications for understanding the cardiovascular outcomes associated with the clinical use of this drug.     

Effect of hypoxia on arterial baroreflex control of heart rate and muscle sympathetic nerve activity in humans.

We tested the hypothesis that acute hypoxia would alter the sensitivity of arterial baroreflex control of both heart rate and sympathetic vasoconstrictor outflow. In 16 healthy, nonsmoking, normotensive subjects (8 women, 8 men, age 20-33 yr), we assessed baroreflex control of heart rate and muscle sympathetic nerve activity by using the modified Oxford technique during both normoxia and hypoxia (12% O(2)). Compared with normoxia, hypoxia reduced arterial O(2) saturation levels from 96.8 +/- 0.3 to 80.7 +/- 1.4% (P < 0.001), increased heart rate from 59.8 +/- 2.4 to 79.4 +/- 2.9 beats/min (P < 0.001), increased mean arterial pressure from 96.7 +/- 2.5 to 105.0 +/- 3.3 mmHg (P = 0.002), and increased sympathetic activity 126 +/- 58% (P < 0.05). The sensitivity for baroreflex control of both heart rate and sympathetic activity was not altered by hypoxia (heart rate: -1.02 +/- 0.09 vs. -1.02 +/- 0.11 beats. min(-1). mmHg(-1); nerve activity: -5.6 +/- 0.9 vs. -6.2 +/- 0.9 integrated activity. beat(-1). mmHg(-1); both P > 0.05). Acute exposure to hypoxia reset baroreflex control of both heart rate and sympathetic activity to higher pressures without changes in baroreflex sensitivity.     

Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients.

The arterial baroreflex buffers slow (<0.05 Hz) blood pressure (BP) fluctuations, mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an important characteristic of baroreflex control, is often noninvasively assessed by relating heart rate (HR) fluctuations to BP fluctuations; more specifically, spectral BRS assessment techniques focus on the BP-to-HR transfer function around 0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated BP buffering is based on two considerations: 1) baroreflex-modulated peripheral vasomotor function is not necessarily related to baroreflex-HR transfer; and 2) although BP fluctuations around 0.1 Hz (Mayer waves) might be related to baroreflex BP buffering, they are merely a not-intended side effect of a closed-loop control system. To further investigate the relationship between BRS and baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP control to simulate normal subjects and heart failure patients. Output variables for various randomly chosen combinations of feedback gains in the baroreflex arms were BP resonance, BP-buffering capacity, and BRS. Our results show that BP buffering and BP resonance are related expressions of baroreflex BP control and depend strongly on the sympathetic gain to the peripheral resistance. BRS is almost uniquely determined by the vagal baroreflex gain to the sinus node. In conclusion, BP buffering and BRS are unrelated unless coupled gains in all baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most likely to be attributed to vagal effects on the heart instead of to effective BP buffering.     

Gender difference in baroreflex-mediated bradycardia in young rats: role of cardiac sympathetic and parasympathetic components.

In a previous clinical study we have demonstrated a significantly lower baroreflex-mediated bradycardic response in young women compared with men. The present study determined whether sexual dimorphism in baroreflex sensitivity in young rats also covers the reflex tachycardic response. The study was then extended to test the hypothesis that an attenuated cardiac cholinergic component of the baroreflex heart rate response in females may account for the gender difference. Baroreflex sensitivity (BRS) was expressed as the regression coefficient of the reciprocal relationship between evoked changes in blood pressure and heart rate. BRS measured in conscious rats with phenylephrine (BRS(PE)) and nitroprusside (BRS(NP)) represented the reflex bradycardic and tachycardic responses, respectively. Female rats exhibited significantly lower BRS(PE) compared with male rats (-1.53+/-0.1 vs. -2.36+/-0.13 beats x min(-1) x mmHg(-1); p < 0.05) but similar BRS(NP) (-2.60+/-0.20 vs. -2.29+/-0.17 beats x min(-1) x mmHg(-1)). Blockade of cardiac muscarinic receptors with atropine methyl bromide elicited greater attenuation of BRS(PE) in male than in female rats (72+/-4.6 vs. 53+/-6.7% inhibition; p < 0.01) and abolished the gender difference. In male rats cardiac muscarinic blockade attenuated BRS(PE) significantly more than did cardiac beta-adrenergic receptor blockade with propranolol (72+/-4.6 vs. 43+/-2.7; p < 0.01), which suggests greater dependence of BRS(PE) on the parasympathetic component. In females, muscarinic and beta-adrenergic blockade elicited similar attenuation of BRS(PE). The findings suggest that (i) BRS is differentially influenced by gender; female rats exhibit substantially lower BRS(PE) but similar BRS(NP) compared with age-matched male rats and (ii) the sexual dimorphism in BRS(PE) results, at least partly, from a smaller increase in vagal outflow to the heart in response to baroreceptor activation.     

Attenuation of sympathetic baroreflex sensitivity during the onset of acute mental stress in humans

Mental stress consistently induces a pressor response that is often accompanied by a paradoxical increase of muscle sympathetic nerve activity (MSNA). The purpose of the present study was to evaluate sympathetic baroreflex sensitivity (BRS) by examining the relations between spontaneous fluctuations of diastolic arterial pressure (DAP) and MSNA. We hypothesized that sympathetic BRS would be attenuated during mental stress. DAP and MSNA were recorded during 5 min of supine baseline, 5 min of mental stress, and 5 min of recovery in 32 young healthy adults. Burst incidence and area were determined for each cardiac cycle and placed into 3-mmHg DAP bins; the slopes between DAP and MSNA provided an index of sympathetic BRS. Correlations between DAP and MSNA were strong (> 0.5) during baseline in 31 of 32 subjects, but we evaluated the change in slope only for those subjects maintaining a strong correlation during mental stress (16 subjects). During baseline, the relation between DAP and MSNA was negative when expressed as either burst incidence [slope = -1.95 ± 0.18 bursts·(100 beats)?1)·mmHg?1; r = -0.86 ± 0.03] or total MSNA [slope = -438 ± 91 units·(beat)?1 mmHg?1; r = -0.76 ± 0.06]. During mental stress, the slope between burst incidence and DAP was significantly reduced [slope = -1.14 ± 0.12 bursts·(100 beats)?1·mmHg?1; r = -0.72 ± 0.03; P < 0.01], indicating attenuation of sympathetic BRS. A more detailed analysis revealed an attenuation of sympathetic BRS during the first 2 min of mental stress (P < 0.01) but no change during the final 3 min of mental stress (P = 0.25). The present study demonstrates that acute mental stress attenuates sympathetic BRS, which may partially contribute to sympathoexcitation during the mental stress-pressor response. However, this attenuation appears to be isolated to the onset of mental stress. Moreover, variable MSNA responses to mental stress do not appear to be directly related to sympathetic BRS.     

GABA in the paraventricular nucleus tonically suppresses baroreflex function: alterations during pregnancy

It is well established that GABAergic inputs to the paraventricular nucleus of the hypothalamus (PVN) tonically suppress heart rate and the activity of several sympathetic nerves. However, whether GABA similarly inhibits PVN control of baroreflex function has not been previously investigated. To test this hypothesis, it was determined whether microinjection of the GABA(A) antagonist, bicuculline, into the PVN enhances the baroreflex in anesthetized female virgin rats. In addition, because GABAergic inhibition of PVN preautonomic neurons is decreased during pregnancy, it was also determined whether the effects of PVN bicuculline administration on baroreflex function were less in pregnant animals. In virgin rats, PVN microinjection of bicuculline increased (P < 0.05) baroreflex gain and maximum levels of heart rate (gain, from 1.6 ± 0.6 to 3.8 ± 1.3 bpm/mmHg; maximum, from 406 ± 18 to 475 ± 14 bpm) and of lumbar sympathetic nerve activity (gain from 2.6 ± 0.7 to 4.8 ± 1.6%/mmHg; maximum, 149 ± 32 to 273 ± 48%), indicating that PVN GABA normally suppresses baroreflex function. Pregnancy decreased heart rate baroreflex gain (pregnant, 0.9 ± 0.3 bpm/mmHg; virgin, 1.9 ± 0.2 bpm/mmHg; P < 0.05). Following PVN bicuculline administration in pregnant rats, smaller (P < 0.01) increments in baroreflex gain (pregnant, 0.6 ± 0.1 bpm/mmHg; virgin, 2.4 ± 0.9 bpm/mmHg) and maximum (pregnant, 33 ± 7 bpm; virgin, 75 ± 12 bpm; P < 0.05) were produced. Collectively, these data suggest that the PVN normally inhibits the baroreflex via tonic GABAergic inputs and that this inhibition is less during pregnancy.     

Age dependency of cardiovascular autonomic responses to head-up tilt in healthy subjects.

In elderly subjects, heart rate responses to postural change are attenuated, whereas their vascular responses are augmented. Altered strategy in maintaining blood pressure homeostasis during upright position may result from various cardiovascular changes, including age-related cardiovascular autonomic dysfunction. This exploratory study was conducted to evaluate impact of age on cardiovascular autonomic responses to head-up tilt (HUT) in healthy subjects covering a wide age range. The study population consisted of 63 healthy, normal-weight, nonsmoking subjects aged 23-77 yr. Five-minute electrocardiogram and finger blood pressure recordings were performed in the supine position and in the upright position 5 min after 70 degrees HUT. Stroke volume was assessed from noninvasive blood pressure signals by the arterial pulse contour method. Heart rate variability (HRV) and systolic blood pressure variability (SBPV) were analyzed by using spectral analysis, and baroreflex sensitivity (BRS) was assessed by using sequence and cross-spectral methods. Cardiovascular autonomic activation during HUT consisted of decreases in HRV and BRS and an increase in SBPV. These changes became attenuated with aging. Age correlated significantly with amplitude of HUT-stimulated response of the high-frequency component (r = -0.61, P < 0.001) and the ratio of low-frequency to high-frequency power of HRV (r = -0.31, P < 0.05) and indexes of BRS (local BRS: r = -0.62, P < 0.001; cross-spectral baroreflex sensitivity in the low-frequency range: r = -0.38, P < 0.01). Blood pressure in the upright position was maintained well irrespective of age. However, the HUT-induced increase in heart rate was more pronounced in the younger subjects, whereas the increase in peripheral resistance was predominantly observed in the older subjects. Thus it is likely that whereas the dynamic capacity of cardiac autonomic regulation decreases, vascular responses related to vasoactive mechanisms and vascular sympathetic regulation become augmented with increasing age.     

Altered autonomic cardiac regulation in individuals with Down syndrome

We tested the hypothesis that individuals with Down syndrome, but without congenital heart disease, exhibit altered autonomic cardiac regulation. Ten subjects with Down syndrome (DS) and ten gender-and age-matched healthy control subjects were studied at rest and during active orthostatism, which induces reciprocal changes in sympathetic and parasympathetic traffic to the heart. Autoregressive power spectral analysis was used to investigate R-R interval variability. Baroreflex modulation of sinus node was assessed by the spontaneous baroreflex sequences method. No significant differences between DS and control subjects were observed in arterial blood pressure at rest or in response to standing. Also, R-R interval did not differ at rest. R-R interval decreased significantly less during standing in DS vs. control subjects. Low-frequency (LFNU) and high-frequency (HFNU) (both expressed in normalized units) components of R-R interval variability did not differ between DS and control subjects at rest. During standing, significant increase in LFNU and decrease in HFNU were observed in control subjects but not in DS subjects. Baroreflex sensitivity (BRS) did not differ between DS and control subjects at rest and underwent significant decrease on going from supine to upright in both groups. However, BRS was greater in DS vs. control subjects during standing. These data indicate that subjects with DS exhibit reduced HR response to orthostatic stress associated with blunted sympathetic activation and vagal withdrawal and with a lesser reduction in BRS in response to active orthostatism. These findings suggest overall impairment in autonomic cardiac regulation in DS and may help to explain the chronotropic incompetence typically reported during exercise in subjects with DS without congenital heart disease.     

Arterial baroreflex function is an important determinant of acute cerebral ischemia in rats with middle cerebral artery occlusion

AIMS: To clarify whether arterial baroreflex function is an important determinant of acute cerebral ischemia in rats. MAIN METHODS: Three animal models were used in this study. In the first, saponin conjugated with substance P (SP-SAP) was injected into the nucleus tractus solitarii (NTS) of Sprague-Dawley (SD) rats to block the central baroreflex arc. In the second model, sinoaortic denervation (SAD) was performed to destroy the peripheral baroreflex arc in SD rats. In the third model, SD rats were divided into two groups according to their naturally occurring BRS values. After determining hemodynamic indexes and baroreflex sensitivity (BRS), we subjected the animals to middle cerebral artery (MCA) occlusion. Levels of interleukin (IL)-1beta and IL-6 were detected both in SAD/sham operation groups and low/high BRS groups. KEY FINDINGS: In all three animal models, baroreflex dysfunction significantly increased the infarct volume and weight. The levels of inflammatory factors were markedly elevated in SAD and low BRS groups. SIGNIFICANCE: These results demonstrate that the function of arterial baroreflex is an important determinant of acute cerebral ischemia in rats with MCA occlusion. Inflammation might be an important mechanism for the arterial baroreflex dysfunction-induced increase in brain damage in rats with MCA occlusion.