Effect of carotid and aortic baroreceptors on cardiopulmonary reflex: the role of autonomic function.

We determined the sympathetic and parasympathetic control of heart rate (HR) and the sensitivity of the cardiopulmonary receptors after selective carotid and aortic denervation. We also investigated the participation of the autonomic nervous system in the Bezold-Jarish reflex after selective removal of aortic and carotid baroreceptors. Male Wistar rats (220-270 g) were divided into three groups: control (CG, N = 8), aortic denervation (AG, N = 5) and carotid denervation (CAG, N = 9). AG animals presented increased arterial pressure (12%) and HR (11%) compared with CG, while CAG animals presented a reduction in arterial pressure (16%) and unchanged HR compared with CG. The sequential blockade of autonomic effects by atropine and propranolol indicated a reduction in vagal function in CAG (a 50 and 62% reduction in vagal effect and tonus, respectively) while AG showed an increase of more than 100% in sympathetic control of HR. The Bezold-Jarish reflex was evaluated using serotonin, which induced increased bradycardia and hypotension in AG and CAG, suggesting that the sensitivity of the cardiopulmonary reflex is augmented after selective denervation. Atropine administration abolished the bradycardic responses induced by serotonin in all groups; however, the hypotensive response was still increased in AG. Although the responses after atropine were lower than the responses before the drug, indicating a reduction in vagal outflow after selective denervation, our data suggest that both denervation procedures are associated with an increase in sympathetic modulation of the vessels, indicating that the sensitivity of the cardiopulmonary receptors was modulated by baroreceptor fibers.

Effect of carotid and aortic baroreceptors on cardiopulmonary reflex: the role of autonomic function

We determined the sympathetic and parasympathetic control of heart rate (HR) and the sensitivity of the cardiopulmonary receptors after selective carotid and aortic denervation. We also investigated the participation of the autonomic nervous system in the Bezold-Jarish reflex after selective removal of aortic and carotid baroreceptors. Male Wistar rats (220-270 g) were divided into three groups: control (CG, N = 8), aortic denervation (AG, N = 5) and carotid denervation (CAG, N = 9). AG animals presented increased arterial pressure (12 percent) and HR (11 percent) compared with CG, while CAG animals presented a reduction in arterial pressure (16 percent) and unchanged HR compared with CG. The sequential blockade of autonomic effects by atropine and propranolol indicated a reduction in vagal function in CAG (a 50 and 62 percent reduction in vagal effect and tonus, respectively) while AG showed an increase of more than 100 percent in sympathetic control of HR. The Bezold-Jarish reflex was evaluated using serotonin, which induced increased bradycardia and hypotension in AG and CAG, suggesting that the sensitivity of the cardiopulmonary reflex is augmented after selective denervation. Atropine administration abolished the bradycardic responses induced by serotonin in all groups; however, the hypotensive response was still increased in AG. Although the responses after atropine were lower than the responses before the drug, indicating a reduction in vagal outflow after selective denervation, our data suggest that both denervation procedures are associated with an increase in sympathetic modulation of the vessels, indicating that the sensitivity of the cardiopulmonary receptors was modulated by baroreceptor fibers.

Baroreflex deficit blunts exercise training-induced cardiovascular and autonomic adaptations in hypertensive rats.

1. Baroreceptors regulate moment-to-moment blood pressure (BP) variations, but their long-term effect on the cardiovascular system remains unclear. Baroreceptor deficit accompanying hypertension contributes to increased BP variability (BPV) and sympathetic activity, whereas exercise training has been associated with an improvement in these baroreflex-mediated changes. The aim of the present study was to evaluate the autonomic, haemodynamic and cardiac morphofunctional effects of long-term sinoaortic baroreceptor denervation (SAD) in trained and sedentary spontaneously hypertensive rats (SHR). 2. Rats were subjected to SAD or sham surgery and were then further divided into sedentary and trained groups. Exercise training was performed on a treadmill (five times per week, 50-70% maximal running speed). All groups were studied after 10 weeks. 3. Sinoaortic baroreceptor denervation in SHR had no effect on basal heart rate (HR) or BP, but did augment BPV, impairing the cardiac function associated with increased cardiac hypertrophy and collagen deposition. Exercise training reduced BP and HR, re-established baroreflex sensitivity and improved both HR variability and BPV. However, SAD in trained SHR blunted all these improvements. Moreover, the systolic and diastolic hypertensive dysfunction, reduced left ventricular chamber diameter and increased cardiac collagen deposition seen in SHR were improved after the training protocol. These benefits were attenuated in trained SAD SHR. 4. In conclusion, the present study has demonstrated that the arterial baroreflex mediates cardiac disturbances associated with hypertension and is crucial for the beneficial cardiovascular morphofunctional and autonomic adaptations induced by chronic exercise in hypertension.

Evidence that blood pressure remains under the control of arterial baroreceptors in renal hypertensive rats

The purpose of the present study was to determine the range of the influence of the baroreflex on blood pressure in chronic renal hypertensive rats. Supramaximal electrical stimulation of the aortic depressor nerve and section of the baroreceptor nerves (sinoaortic denervation) were used to obtain a global analysis of the baroreceptor-sympathetic reflex in normotensive control and in chronic (2 months) 1-kidney, 1-clip hypertensive rats. The fall in blood pressure produced by electrical baroreceptor stimulation was greater in renal hypertensive rats than in normotensive controls (right nerve: -47 ± 8 vs -23 ± 4 mmHg; left nerve: -51 ± 7 vs -30 ± 4 mmHg; and both right and left nerves: -50 ± 8 vs -30 ± 4 mmHg; P < 0.05). Furthermore, the increase in blood pressure level produced by baroreceptor denervation in chronic renal hypertensive rats was similar to that observed in control animals 2-5 h (control: 163 ± 5 vs 121 ± 1 mmHg; 1K-1C: 203 ± 7 vs 170 ± 5 mmHg; P < 0.05) and 24 h (control: 149 ± 3 vs 121 ± 1 mmHg; 1K-1C: 198 ± 8 vs 170 ± 5 mmHg; P < 0.05) after sinoaortic denervation. Taken together, these data indicate that the central and peripheral components of the baroreflex are acting efficiently at higher arterial pressure in renal hypertensive rats when the aortic nerve is maximally stimulated or the activity is abolished.

Evidence that blood pressure remains under the control of arterial baroreceptors in renal hypertensive rats.

The purpose of the present study was to determine the range of the influence of the baroreflex on blood pressure in chronic renal hypertensive rats. Supramaximal electrical stimulation of the aortic depressor nerve and section of the baroreceptor nerves (sinoaortic denervation) were used to obtain a global analysis of the baroreceptor-sympathetic reflex in normotensive control and in chronic (2 months) 1-kidney, 1-clip hypertensive rats. The fall in blood pressure produced by electrical baroreceptor stimulation was greater in renal hypertensive rats than in normotensive controls (right nerve: -47 +/- 8 vs -23 +/- 4 mmHg; left nerve: -51 +/- 7 vs -30 +/- 4 mmHg; and both right and left nerves: -50 +/- 8 vs -30 +/- 4 mmHg; P < 0.05). Furthermore, the increase in blood pressure level produced by baroreceptor denervation in chronic renal hypertensive rats was similar to that observed in control animals 2-5 h (control: 163 +/- 5 vs 121 +/- 1 mmHg; 1K-1C: 203 +/- 7 vs 170 +/- 5 mmHg; P < 0.05) and 24 h (control: 149 +/- 3 vs 121 +/- 1 mmHg; 1K-1C: 198 +/- 8 vs 170 +/- 5 mmHg; P < 0.05) after sinoaortic denervation. Taken together, these data indicate that the central and peripheral components of the baroreflex are acting efficiently at higher arterial pressure in renal hypertensive rats when the aortic nerve is maximally stimulated or the activity is abolished.

Critical analysis of autoregressive and fast Fourier transform markers of cardiovascular variability in rats and humans

The autonomic nervous system plays an important role in physiological and pathological conditions, and has been extensively evaluated by parametric and non-parametric spectral analysis. To compare the results obtained with fast Fourier transform (FFT) and the autoregressive (AR) method, we performed a comprehensive comparative study using data from humans and rats during pharmacological blockade (in rats), a postural test (in humans), and in the hypertensive state (in both humans and rats). Although postural hypotension in humans induced an increase in normalized low-frequency (LFnu) of systolic blood pressure, the increase in the ratio was detected only by AR. In rats, AR and FFT analysis did not agree for LFnu and high frequency (HFnu) under basal conditions and after vagal blockade. The increase in the LF/HF ratio of the pulse interval, induced by methylatropine, was detected only by FFT. In hypertensive patients, changes in LF and HF for systolic blood pressure were observed only by AR; FFT was able to detect the reduction in both blood pressure variance and total power. In hypertensive rats, AR presented different values of variance and total power for systolic blood pressure. Moreover, AR and FFT presented discordant results for LF, LFnu, HF, LF/HF ratio, and total power for pulse interval. We provide evidence for disagreement in 23 percent of the indices of blood pressure and heart rate variability in humans and 67 percent discordance in rats when these variables are evaluated by AR and FFT under physiological and pathological conditions. The overall disagreement between AR and FFT in this study was 43 percent.

Critical analysis of autoregressive and fast Fourier transform markers of cardiovascular variability in rats and humans.

The autonomic nervous system plays an important role in physiological and pathological conditions, and has been extensively evaluated by parametric and non-parametric spectral analysis. To compare the results obtained with fast Fourier transform (FFT) and the autoregressive (AR) method, we performed a comprehensive comparative study using data from humans and rats during pharmacological blockade (in rats), a postural test (in humans), and in the hypertensive state (in both humans and rats). Although postural hypotension in humans induced an increase in normalized low-frequency (LFnu) of systolic blood pressure, the increase in the ratio was detected only by AR. In rats, AR and FFT analysis did not agree for LFnu and high frequency (HFnu) under basal conditions and after vagal blockade. The increase in the LF/HF ratio of the pulse interval, induced by methylatropine, was detected only by FFT. In hypertensive patients, changes in LF and HF for systolic blood pressure were observed only by AR; FFT was able to detect the reduction in both blood pressure variance and total power. In hypertensive rats, AR presented different values of variance and total power for systolic blood pressure. Moreover, AR and FFT presented discordant results for LF, LFnu, HF, LF/HF ratio, and total power for pulse interval. We provide evidence for disagreement in 23% of the indices of blood pressure and heart rate variability in humans and 67% discordance in rats when these variables are evaluated by AR and FFT under physiological and pathological conditions. The overall disagreement between AR and FFT in this study was 43%.

Increased sympathetic activity in normotensive offspring of malignant hypertensive parents compared to offspring of normotensive parents.

Malignant hypertension seems to be the consequence of very high blood pressure. Furthermore, an increase in sympathetic and renin-angiotensin system activity is considered to be the main mechanisms producing malignant hypertension. In the present study, 10 offspring of malignant hypertensive (OMH) parents (age 28 +/- 5 years, 7 males, 3 females, 2 white and 8 non-white) and 10 offspring of normotensive (ONT) parents (age 28 +/- 6 years, 2 males, 8 females, 3 white and 7 non-white) were evaluated. The OMH group had significantly higher (P < 0.05) casual blood pressure (125 +/- 10/81 +/- 5 mmHg) compared with ONT (99 +/- 13/67 +/- 5 mmHg). The increase in blood pressure was greater in OMH (Delta SBP = 17 +/- 2 vs Delta SBP = 9 +/- 1 mmHg in ONT) during cold pressor testing, but they had a lower increase in heart rate (Delta HR = 13 +/- 2 vs Delta HR = 20 +/- 3 bpm in ONT) during isometric exercise(handgrip test). Sympathetic activity, measured by microneurography, was significantly higher (P < 0.05) before exercise in OMH (17 +/- 6 vs 11 +/- 4 burst/min in ONT) and exhibited a greater increase (Delta = 18 +/- 10 vs Delta = 8 +/- 3 burst/min in ONT) during isometric exercise. This study showed increased sympathetic activity in OMH before exercise and a greater response during isometric exercise, suggesting an autonomic abnormality before exercise and a greater sympathetic response to physical stress in OMH compared to ONT.

Increased sympathetic activity in normotensive offspring of malignant hypertensive parents compared to offspring of normotensive parents

Malignant hypertension seems to be the consequence of very high blood pressure. Furthermore, an increase in sympathetic and renin-angiotensin system activity is considered to be the main mechanisms producing malignant hypertension. In the present study, 10 offspring of malignant hypertensive (OMH) parents (age 28 ± 5 years, 7 males, 3 females, 2 white and 8 non-white) and 10 offspring of normotensive (ONT) parents (age 28 ± 6 years, 2 males, 8 females, 3 white and 7 non-white) were evaluated. The OMH group had significantly higher (P < 0.05) casual blood pressure (125 ± 10/81 ± 5 mmHg) compared with ONT (99 ± 13/67 ± 5 mmHg). The increase in blood pressure was greater in OMH (Ä SBP = 17 ± 2 vs Ä SBP = 9 ± 1 mmHg in ONT) during cold pressor testing, but they had a lower increase in heart rate (Ä HR = 13 ± 2 vs Ä HR = 20 ± 3 bpm in ONT) during isometric exercise (handgrip test). Sympathetic activity, measured by microneurography, was significantly higher (P < 0.05) before exercise in OMH (17 ± 6 vs 11 ± 4 burst/min in ONT) and exhibited a greater increase (Ä = 18 ± 10 vs Ä = 8 ± 3 burst/min in ONT) during isometric exercise. This study showed increased sympathetic activity in OMH before exercise and a greater response during isometric exercise, suggesting an autonomic abnormality before exercise and a greater sympathetic response to physical stress in OMH compared to ONT.

Acute water ingestion increases arterial blood pressure in hypertensive and normotensive subjects.

In patients with severe autonomic dysfunction, water ingestion elicits an acute pressor response. Hypertension may be associated with changes in cardiovascular autonomic modulation, but there is no information on the acute effects of water ingestion in patients with hypertension. In this study, we compared the effect of acute water ingestion on haemodynamic and autonomic responses of hypertensive and normotensive individuals. Eight patients with mild hypertension were compared to 10 normotensive individuals. After 30 min resting in the supine position all subjects ingested 500 ml of water. At baseline and after water ingestion, venous blood samples for plasma volume determination were collected, and electrocardiographic tracings, finger blood pressure, forearm blood flow and muscle sympathetic nerve activity (MSNA) were obtained. Water ingestion resulted in similar and minor reduction in plasma volume. Systolic and diastolic blood pressure increased in both hypertensive (mean+/-s.d.: 19/14+/-6/3 mm Hg) and normotensive subjects (17/14+/-6/3 mm Hg). There was an increase in forearm vascular resistance and in MSNA. Heart rate was reduced (hypertensive: 5+/-1 beats/min, normotensive: 5+/-6 beats/min) and the high-frequency component of heart rate and systolic blood pressure variability was increased. In hypertensive and normotensive individuals, acute water ingestion elicits a pressor response, an effect that is most likely determined by an increased vasoconstrictor sympathetic activity, and is counterbalanced by an increase in blood pressure and heart rate vagal modulation.

Influence of cardiopulmonary reflex on the sympathetic activity during myocardial infarction.

The time-course of changes in renal sympathetic nerve activity (RSNA), arterial and cardiopulmonary baroreflexes sensitivities was evaluated in conscious rats eight hours (8 h) and ten days (10 day) after myocardial infarction (MI), induced by coronary artery ligation. RSNA was recorded by a platinum electrode implanted in left renal nerve. Arterial and cardiopulmonary baroreflexes sensitivities were evaluated by changes in blood pressure and serotonin administration, respectively. Both 8 h and 10 day groups presented hypotension (103+/-4 vs. 102+/-2 vs. 115+/-4 mm Hg), but only 8 h showed tachycardia (422+/-22 vs. 378+/-11 vs. 384+/-9 bpm) when compared to Control rats. RSNA was depressed 8 h after MI and increased in 10 day group (12+/-2 vs. 39+/-8 vs. 22+/-2 mV/cycle). Although arterial baroreflex control of heart rate was similar in all groups, the arterial baroreflex control of RSNA in 8 h group was impaired during reductions (-0.35+/-0.10 vs. -1.66+/-0.23 vs. -0.09+/-0.14 mV/cycle/mm Hg) or increases (-0.77+/-0.17 vs. -1.63+/-0.58 vs. -1.66+/-0.17 mV/cycle/mm Hg) in blood pressure when compared to Control animals. Moreover, cardiopulmonary baroreflex bradycardic response was increased in 8 h rats and normalized in 10 day group. The results suggest that the increased cardiopulmonary baroreflex sensitivity in 8 h may contribute to the reduction in the tonic level of RSNA as well as in the impairment of the baroreflex control of RSNA in the presence of hypotension.

Phenotypic characteristics associated with hypertension in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) causes secondary hypertension. However, the reasons why the prevalence of hypertension among OSA patients varies widely (35-70%) are not clear. We sought to investigate the phenotypic characteristics of patients with and without hypertension among OSA patients who were matched for disease severity. We studied 152 OSA patients (76 normotensive and 76 hypertensive) diagnosed by polysomnography. Detailed phenotypic characteristics, including laboratorial analysis, were determined in all patients. Univariate analysis followed by multiple logistic regression analysis was used to identify variables that were independently associated with hypertension. The apnea-hypopnea index in normotensive and hypertensive patients was similar (48+/-26 and 48+/-26 events/h, respectively) as well as minimum arterial oxygen saturation (76+/-10 and 75+/-10%, respectively) and total sleep time with oxyhaemoglobin saturation <90% (25+/-25 and 28+/-26%, respectively). Hypertensive patients were older (57+/-11 vs 47+/-12 years; P<0.001), had a higher body mass index (BMI; 34+/-7 vs 30+/-5 kg/m(2); P<0.001), had a higher frequency of women (37 vs 8%; P<0.001), had a higher incidence of diabetes (25 vs 6%; P=0.002) and a higher family history of hypertension (75 vs 42%; P=0.01) than did the normotensive patients. Multiple logistic regression analysis indicated that age (P=0.004), familial history of hypertension (P=0.004), BMI (P=0.04) and female sex (P=0.03) were the independent variables associated with hypertension. We concluded that increasing age and BMI, familial history of hypertension as well as female gender are phenotypic characteristics associated with hypertension among OSA patients with similar disease severity.

A semi-automatic computerized method to measure baroreflex-mediated heart rate responses that reduces interobserver variability.

Arterial baroreflex sensitivity estimated by pharmacological impulse stimuli depends on intrinsic signal variability and usually a subjective choice of blood pressure (BP) and heart rate (HR) values. We propose a semi-automatic method to estimate cardiovascular reflex sensitivity to bolus infusions of phenylephrine and nitroprusside. Beat-to-beat BP and HR time series for male Wistar rats (N = 13) were obtained from the digitized signal (sample frequency = 2 kHz) and analyzed by the proposed method (PRM) developed in Matlab language. In the PRM, time series were low-pass filtered with zero-phase distortion (3rd order Butterworth used in the forward and reverse direction) and presented graphically, and parameters were selected interactively. Differences between basal mean values and peak BP (deltaBP) and HR (deltaHR) values after drug infusions were used to calculate baroreflex sensitivity indexes, defined as the deltaHR/deltaBP ratio. The PRM was compared to the method traditionally (TDM) employed by seven independent observers using files for reflex bradycardia (N = 43) and tachycardia (N = 61). Agreement was assessed by Bland and Altman plots. Dispersion among users, measured as the standard deviation, was higher for TDM for reflex bradycardia (0.60 +/- 0.46 vs 0.21 +/- 0.26 bpm/mmHg for PRM, P < 0.001) and tachycardia (0.83 +/- 0.62 vs 0.28 +/- 0.28 bpm/mmHg for PRM, P < 0.001). The advantage of the present method is related to its objectivity, since the routine automatically calculates the desired parameters according to previous software instructions. This is an objective, robust and easy-to-use tool for cardiovascular reflex studies.

A semi-automatic computerized method to measure baroreflex-mediated heart rate responses that reduces interobserver variability

Arterial baroreflex sensitivity estimated by pharmacological impulse stimuli depends on intrinsic signal variability and usually a subjective choice of blood pressure (BP) and heart rate (HR) values. We propose a semi-automatic method to estimate cardiovascular reflex sensitivity to bolus infusions of phenylephrine and nitroprusside. Beat-to-beat BP and HR time series for male Wistar rats (N = 13) were obtained from the digitized signal (sample frequency = 2 kHz) and analyzed by the proposed method (PRM) developed in Matlab language. In the PRM, time series were low-pass filtered with zero-phase distortion (3rd order Butterworth used in the forward and reverse direction) and presented graphically, and parameters were selected interactively. Differences between basal mean values and peak BP (deltaBP) and HR (deltaHR) values after drug infusions were used to calculate baroreflex sensitivity indexes, defined as the deltaHR/deltaBP ratio. The PRM was compared to the method traditionally (TDM) employed by seven independent observers using files for reflex bradycardia (N = 43) and tachycardia (N = 61). Agreement was assessed by Bland and Altman plots. Dispersion among users, measured as the standard deviation, was higher for TDM for reflex bradycardia (0.60 ± 0.46 vs 0.21 ± 0.26 bpm/mmHg for PRM, P < 0.001) and tachycardia (0.83 ± 0.62 vs 0.28 ± 0.28 bpm/mmHg for PRM, P < 0.001). The advantage of the present method is related to its objectivity, since the routine automatically calculates the desired parameters according to previous software instructions. This is an objective, robust and easy-to-use tool for cardiovascular reflex studies.

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy.

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.

Pressure and time dependence of the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy

The first minutes of the time course of cardiopulmonary reflex control evoked by lower body negative pressure (LBNP) in patients with hypertensive cardiomyopathy have not been investigated in detail. We studied 15 hypertensive patients with left ventricular dysfunction (LVD) and 15 matched normal controls to observe the time course response of the forearm vascular resistance (FVR) during 3 min of LBNP at -10, -15, and -40 mmHg in unloading the cardiopulmonary receptors. Analysis of the average of 3-min intervals of FVR showed a blunted response of the LVD patients at -10 mmHg (P = 0.03), but a similar response in both groups at -15 and -40 mmHg. However, using a minute-to-minute analysis of the FVR at -15 and -40 mmHg, we observed a similar response in both groups at the 1st min, but a marked decrease of FVR in the LVD group at the 3rd min of LBNP at -15 mmHg (P = 0.017), and -40 mmHg (P = 0.004). Plasma norepinephrine levels were analyzed as another neurohumoral measurement of cardiopulmonary receptor response to LBNP, and showed a blunted response in the LVD group at -10 (P = 0.013), -15 (P = 0.032) and -40 mmHg (P = 0.004). We concluded that the cardiopulmonary reflex response in patients with hypertensive cardiomyopathy is blunted at lower levels of LBNP. However, at higher levels, the cardiopulmonary reflex has a normal initial response that decreases progressively with time. As a consequence of the time-dependent response, the cardiopulmonary reflex response should be measured over small intervals of time in clinical studies.

Exercise training changes autonomic cardiovascular balance in mice.

Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of heart rate were measured in conscious, unrestrained male C57/6J sedentary (n = 8) and trained mice (n = 8). The exercise training protocol used a treadmill (1 h/day; 5 days/wk for 4 wk). Baroreflex sensitivity was evaluated by the tachycardic and bradycardic responses induced by sodium nitroprusside and phenylephrine, respectively. Autonomic control of heart rate and intrinsic heart rate were determined by use of methylatropine and propranolol. Resting bradycardia was observed in trained mice compared with sedentary animals [485 +/- 9 vs. 612 +/- 5 beats/min (bpm)], whereas mean arterial pressure was not different between the groups (106 +/- 2 vs. 108 +/- 3 mmHg). Baroreflex-mediated tachycardia was significantly enhanced in the trained group (6.97 +/- 0.97 vs. 1.6 +/- 0.21 bpm/mmHg, trained vs. sedentary), whereas baroreflex-mediated bradycardia was not altered by training. The tachycardia induced by methylatropine was significantly increased in trained animals (139 +/- 12 vs. 40 +/- 9 bpm, trained vs. sedentary), whereas the propranolol effect was significantly reduced in the trained group (49 +/- 11 vs. 97 +/- 11 bpm, trained vs. sedentary). Intrinsic heart rate was similar between groups. In conclusion, dynamic exercise training in mice induced a resting bradycardia and an improvement in baroreflex-mediated tachycardia. These changes are likely related to an increased vagal and decreased sympathetic tone, similar to the exercise response observed in humans.

Dysregulation of peripheral and central chemoreflex responses in Chagas' heart disease patients without heart failure.

BACKGROUND: The peripheral and central chemoreflexes are important autonomic mechanisms for regulating breathing and cardiovascular function. Although pathological inflammatory infiltration of the peripheral chemoreceptors and central nervous system has been reported in Chagas' disease, functional evaluation of chemoreflexes has not yet been performed. METHODS AND RESULTS: The hypothesis that chemoreflex function is altered in patients with Chagas' heart disease (CH) but normal left ventricle function was tested in 12 CH patients and 13 matched control subjects. The ventilatory rate, minute ventilation, heart rate, mean arterial pressure, forearm blood flow, forearm vascular resistance, and venous norepi-nephrine responses to hypoxia and hypercapnia were determined. During hypoxia, the decrease in oxygen saturation was smaller in CH patients, despite a similar ventilatory response between groups. Both groups showed an increase in heart rate during hypoxia, but this response was blunted in CH patients. Although the mean arterial pressure response to hypoxia was similar in both groups, forearm vascular resistance significantly decreased in control subjects while remaining unchanged in CH patients. Moreover, a significant increase in plasma norepinephrine levels elicited by stimulation of peripheral chemoreceptors was observed only in the CH group. During hypercapnia, the increase in minute ventilation was smaller in CH patients, who did not exhibit the increase in norepinephrine observed in control subjects. CONCLUSIONS: These data suggest that CH potentiates respiratory, cardiovascular, and autonomic responses to peripheral chemoreceptor activation by hypoxia in patients with normal left ventricular function. The ventilatory and sympathetic responses to central chemoreceptor activation by hypercapnia, however, are significantly blunted.

Chronic AT(1) receptor blockade alters autonomic balance and sympathetic responses in hypertension.

In the coarctation hypertension model, we have shown that chronic treatment with losartan causes both normalization of impaired reflex control of heart rate and partial correction of the depressed aortic nerve activity/pressure relationship, even with the persistence of hypertension. In the present study, we analyzed the effects of angiotensin II blockade on the efferent pathways of coarcted and sham-operated groups treated chronically with vehicle or losartan (10 mg/kg per day PO). Hypertension was induced by subdiaphragmatic aortic coarctation, and the treatments lasted 9 days (4 control and 5 experimental days). On day 5, autoregressive power spectral analysis was performed on heart rate recordings made in conscious rats. Other groups were used for sympathetic splanchnic nerve activity recordings made simultaneously with pressure (anesthetized rats) at basal condition and during loading/unloading of baroreceptors. Losartan treatment induced a significant reduction in basal pressure but did not interfere with the development of hypertension (similar pressure increases of 24% and 28% over control values in losartan and vehicle groups, respectively). In vehicle-treated rats, establishment of hypertension was accompanied by a marked change in power spectral density from high- (1.19+/-0.06 Hz, 33+/-6%) to low-frequency components (0,42+/-0.03 Hz, 54+/-6%), with increased low-frequency-to-high-frequency ratio. When compared with sham-operated vehicle-treated rats, there was also increase in the gain of sympathetic activity/pressure relationship, with displacement of lower plateau toward high levels of sympathetic activity. No changes in the power spectral density and sympathetic activity/pressure relationship were observed when hypertension developed in the presence of chronic angiotensin type 1 (AT(1)) receptor blockade. The data suggest that angiotensin II, activated during the establishment of coarctation hypertension, acts via AT(1) receptors to alter sympathovagal balance, facilitating the sympathetic outflow to heart and peripheral circulation during baroreceptors unloading. Data also indicate that the observed effects are not conditioned by preexisting pressure levels.

Hemodynamic and metabolic profile in offspring of malignant hypertensive parents.

Malignant hypertension is a serious form of arterial hypertension in which the physiopathological mechanisms include increased activity of the sympathetic nervous system, renin angiotensin system, and endothelium dysfunction. Family history of hypertension is an important predictive factor for hypertension and is associated with metabolic and hemodynamic abnormalities. Studies of these abnormalities in malignant hypertensive offspring have not yet been published. Therefore, we studied 42 offspring of malignant hypertensive parents (OMH group: age, 22+/-7 years; 23 male subjects; 27 white) and 35 offspring of normotensive parents (ONT group: age, 21+/-4 years; 23 male subjects; 25 white). All subjects had blood pressure <140/90 mm Hg. We evaluated body mass index; office blood pressure; 24-hour ambulatory and continuous beat-to-beat blood pressure monitoring (Finapres); biochemical analysis, including total cholesterol and fractions, triglycerides, glucose, and insulin; and hormonal analysis, including plasma renin activity, aldosterone, and catecholamines. The subjects were also submitted to cold pressure test and handgrip measurements. The body mass index was significantly higher in the OMH group (24+/-5 kg/m(2)) than in the ONT group (22+/-4 kg/m(2)). The OMH group showed significantly higher blood pressure and heart rate in office and Finapres measurements (P<0.05). In 24-hour ambulatory monitoring, the OMH group presented higher 24-hour blood pressure and heart rate, higher blood pressure during the night, and higher heart rate variability during the day compared with those of the ONT group. They also presented lower HDL cholesterol, higher levels of plasma insulin and norepinephrine, and higher insulin-to-glucose ratio (P<0.05) than the ONT group. There were no differences in the other biochemical parameters measured. In conclusion, OMH subjects show early hemodynamic, neurohumoral, and metabolic alterations that are typical of hypertensive metabolic syndrome.