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.

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.

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.

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.

Acute AT1 receptor blockade does not improve the depressed baroreflex in rats with chronic renal hypertension

To assess the role of angiotensin II in the sensitivity of the baroreflex control of heart rate (HR) in normotensive rats (N = 6) and chronically hypertensive rats (1K1C, 2 months, N = 7), reflex changes of HR were evaluated before and after (15 min) the administration of a selective angiotensin II receptor antagonist (losartan, 10 mg/kg, iv). Baseline values of mean arterial pressure (MAP) were higher in hypertensive rats (195 ± 6 mmHg) than in normotensive rats (110 ± 2 mmHg). Losartan administration promoted a decrease in MAP only in hypertensive rats (16 percent), with no changes in HR. During the control period, the sensitivity of the bradycardic and tachycardic responses to acute MAP changes were depressed in hypertensive rats (~70 percent and ~65 percent, respectively) and remained unchanged after losartan administration. Plasma renin activity was similar in the two groups. The present study demonstrates that acute blockade of AT1 receptors with losartan lowers the MAP in chronic renal hypertensive rats without reversal of baroreflex hyposensitivity, suggesting that the impairment of baroreflex control of HR is not dependent on an increased angiotensin II level

Autonomic abnormalities demonstrable in young normotensive subjects who are children of hypertensive parents

Although a slightly elevated office blood pressure (BP) has been reported in several studies, little is known about the prolonged resting blood pressure, heart rate (HR) and baroreflex sensitivity (BRS) of prehypertensive subjects with a family history of hypertension. Office blood pressure, prolonged resting (1 h) BP and HR were measured in 25 young normotensives with a positive family history of hypertension (FH+) and 25 young normotensives with a negative family history of hypertension (FH-), matched for age, sex, and body mass index. After BP and HR measurements, blood samples were collected for the determination of norepinephrine, plasma renin activity and aldosterone levels, and baroreflex sensitivity was then tested. Casual BP, prolonged resting BP and heart rate were significantly higher in the FH+ group (119.9 + or - 11.7/78.5 + or - 8.6 mmHg, 137.3 + or - 12.3/74.4 + or - 7.9 mmHg, 68.5 + or - 8.4 bpm) compared to the FH- group (112.9 + or - 11.4/71.2 + or - 8.3 mmHg, 128.0 + or - 11.8/66.5 + or - 7.4 mmHg, 62.1 + or - 6.0 bpm). Plasma norepinephrine level was significantly higher in the FH+ group (220.1 + or - 104.5 pg/ml) than in the FH- group (169.1 + or - 63.3 pg/ml). Baroreflex sensitivity to tachycardia (0.7 + or - 0.3 vs 1.0 + or - 0.5 bpm/mmHg) was depressed in the FH+ group (P<0.05). The FH+ group exhibited higher casual blood pressure, prolonged resting blood pressure, heart rate and plasma norepinephrine levels than the FH- group (P<0.05), suggesting an increased sympathetic tone in these subjects. The reflex tachycardia was depressed in the FH+ group

Comparison of three methods for the determination of baroreflex sensitivity in conscious rats

Baroreflex sensitivity was studied in the same group of conscious rats using vasoactive drugs (phenylephrine and sodium nitroprusside) administered by three different approaches: 1) bolus injection, 2) steady-state (blood pressure (BP) changes produced in steps), 3) ramp infusion (30 s, brief infusion). The heart rate (HR) responses were evaluated by the mean index (mean ratio of all HR changes and mean arterial pressure (MAP) changes), by linear regression and by the logistic method (maximum gain of the sigmoid curve by a logistic function). The experiments were performed on three consecutive days. Basal MAP and resting HR were similar on all days of the study. Bradycardic responses evaluated by the mean index (-1.5 ñ 0.2, -2.1 ñ 0.2 and -1.6 ñ 0.2 bpm/mmHg) and linear regression (-1.8 ñ 0.3, -1.4 ñ 0.3 and -1.7 ñ 0.2 bpm/mmHg) were similar for all three approaches used to change blood pressure. The tachycardic responses to decreases of MAP were similar when evaluated by linear regression (-3.9 ñ 0.8, -2.1 ñ 0.7 and -3.8 ñ 0.4 bpm/mmHg). However, the tachycardic mean index (-3.1 ñ 0.4, -6.6 ñ 1 and -3.6 5 0.5 bpm/mmHg) was higher when assessed by the steady-state method. The average gain evaluated by logistic function (-3.5 ñ 0.6, -7.6 ñ 1.3 and -3.8 ñ 0.4 bpm/mmHg) was similar to the reflex tachycardic values, but different from the bradycardic values. Since different ways to change BP may alter the afferent baroreceptor function, the MAP changes obtained during short periods of time (up to 30 s: bolus and ramp infusion) are more appropriate to prevent the acute resetting. Assessment of the baroreflex sensitivity by mean index and linear regression permits a separate analysis of gain for reflex bradycardia and reflex tachycardia. Although two values of baroreflex sensitivity cannot be evaluated by a single symmetric logistic function, this method has the advantage of better comparing the baroreflex sensitivity of animals with different basal blood pressures

Baroreflex control of sympathetic activity in experimental hypertension

The arterial baroreceptor reflex system is one of the most powerful and rapidly acting mechanisms for controlling arterial pressure. The purpose of the present review is to discuss data relating sympathetic activity to the baroreflex control of arterial pressure in two different experimental models: neurogenic hypertension by sinoaortic denervation (SAD) and high-renin hypertension by total aortic ligation between the renal arteries in the rat. SAD depresses baroreflex regulation of renal sympathetic activity in both the acute and chronic phases. However, increased sympathetic activity (100 percent) was found only in the acute phase of sinoaortic denervation. In the chronic phase of SAD average discharge normalized but the pattern of discharges was different from that found in controls. High-renin hypertensive rats showed overactivity of the renin angiotensin system and a great depression of the baroreflexes, comparable to the depression observed in chronic sinoaortic denervated rats. However, there were no differences in the average tonic sympathetic activity or changes in the pattern of discharges in high-renin rats. We suggest that the difference in the pattern of discharges may contribute to the increase in arterial pressure lability observed in chronic sinoaortic denervated rats.

Relaçäo temporal entre atividade neurogênica dos pressoreceptores e atividade simpática periférica e labilidade da pressäo arterial / Temporal relation between neurogenic activity of pressoreceptors and peripheral sympathetic activity and arterial pressure lability

O objetivo desse estudo foi avaliar a atividade neurogênica dos pressoreceptores (APR, registrada no nervo aórtico) e a atividade simpática periférica (ASR, registrada no nervo simpático renal), considerando-se a ocorrência e distribuição nos ciclos cardíacos e nas fases sistólica e diastólica. Foram estudados ratos normais anestesiados e ratos acordados submetidos à desnervação sino-aórtica (DSA) nas fases aguda e crônica após a desnervação. Os resultados obtidos sugerem que a falta de sincronismo entre a atividade simpática e os ciclos da pressão arterial contribuem para as alterações encontradas na pressão sanguínea na ausência dos pressoreceptores

Abstract - The aim of this study was to analyze the neurogenic activity of baroreceptors (recorded on the aortic nerve, APR) and peripheral sympathetic activity (recorded on the renal nerve. AsR ) with regard to its occurence and distribution in relation to the cardiac cycle and the systolic and diastolic phases of it. Normal anesthetized rats and awaken sino aortic denervated (SAD) rats were studied. The analysis showed that the existing synchronism between sympathetic activity and arterial pressure pulses found in normal rats was absent in SAD rats. These results suggest that the Jack of synchronism between sympathetic activity and cardiac cycles may contribute to the alterations in blood pressure observed in the absence of baroreceptors

Angiotensin converting activity assessed in vivo is increased in hereditary hypertensive rats

1. The angiotensin converting enzyme (ACE) activity of spontaneously hypertensive (SHR) and spontaneously hypertensive stroke-prone (SHRSP) rats was compared to the ACE activity of normotensive Wistar-Kyoto rats (WKY). 2. ACE activity was assessed indirectly in conscious unrestrained rats using the equipressor response end point to simultaneously calculate the extent of conversion of angiotensin I (AI) to angiotensin II (AII) and the pulmonary degradation of bradykinin (BK). 3. The pulmonary degradation of BK was significantly elevated (99.4%) in SHR rats whereas the elevation was not significant in SHRSP rats (99.2%) compared to WKY rats, even though the pulmonary inactivation of BK in WKY rats was higher (98.6%) than in normotensive Wistar rats (95.6% and 97.5%) previously studied. 4. Blood pressure responsiveness to intra-aortically injected BK (bolus injection and infusion) was markedly increased in SHR and SHRSP rats with no change in reactivity to sodium nitroprusside. 5. Conversion of AI to AII assessed by the equipressor doses of the hormones which produced a 20-mmHg rise in blood pressure was markedly elevated in SHR (86 +/- 4%) and SHRSP (80 +/- 7%) rats when compared to WKY rats (38 +/- 4%). 6. The marked increase in conversion of AI to AII in hypertensive animals, accompanied by an increased pulmonary degradation of BK in SHR rats, suggests that ACE activity is increased in conscious SHR and SHRSP rats and may participate in the genesis of hypertension in this model of genetic hypertension

Vagal and sympathetic control of heart rate during exercise by sedentary and exercise-trained rats

1. The present investigation was undertaken to study the vagal and sympathetic effects of an acute bout of exercise on ten sedentary (S) and nine trained (T) rats. The exercise training was performed 5 times a week for 13 weeks on a motor treadmill, at 1.0 mph, 15% grade for 60 min. 2. Heart rate (HR) was recorded at rest and during exercise, 15% grade at 0.5, 0.8 and 1.0 mph, for 3 min per stage. Vagal and sympathetic effects were studied after the administration of methylatropine (3 mg/kg) and propranolol (4 mg/kg). 3. Exercise training significantly attenuated cardiac acceleration at 0.8 (441 +/- 8 vs 486 +/- 9 bpm in S, P < 0.05) and 1.0 mph (466 +/- 12 vs 508 +/- 6 bpm in S, P < 0.05). The vagal effect was significantly increased in the T group at 0.8 (72 +/- 5 vs 32 +/- 10 bpm in S, P < 0.05) and 1.0 mph (46 +/- 8 vs 15 +/- 7 bpm in S, P < 0.05). The sympathetic effect was significantly decreased in the T group at 0.8 (73 +/- 9 vs 112 +/- 9 bpm in S, P < 0.05) and 1.0 mph (96 +/- 11 vs 125 +/- 7 bpm in S, P < 0.05). The intrinsic HR behavior was not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between renal sympathetic nerve activity and arterial pressure after selective denervation of baroreceptors and chemoreceptors

The relationship between an acute increase in arterial pressure and renal sympathetic nerve activity produced in rats under chloralose anesthesia after carotid and sinoaortic denervation was analyzed by quantifying the nerve activity associated with arterial pressure changes. After sinus denervation there was no change in arterial pressure (125 ñ 2.3 vs 124.6 ñ 5 mmHg, N +6), but the renal sympathetic nerve activity (10.8 ñ 0.9 vs 8.0 ñ 1.1 bars s-1 cycle-1, N+6) was significantly decreased. In spite of this, baroreflex control of renal sympathetic nerve activity was the same as during the control period. After sinoaortic denervation, there were simultaneous increases in arterial pressure (from 124 ñ 2.3 to 188 ñ 6m Hg, N +6) and renal sympathetic nerve activity (from 10.8 ñ 0.9 to 13.7 ñ 2.9 bars s-1 cycle-1) with marked attenuation of the baroreflexes. Spectral analysis of arterial blood pressure after sinus denervation showed a shift of a 1-Hz peak to 0.7 Hz, probably related to a respiratory frequency. The results suggest that after sinoaortic denervation the acute in arterial pressure is only due to aortic denervation

Influence of general anesthetics on baroreflex control of circulation

1. The effects of sodium pentabarbital and alfa-chloralose anesthesia on the barreflex control of ciruclation were studied in groups of 7 to 11 rats. The tests were performed in conscious undisturbed rats and repeated after anesthesia. 2. Pentobarbital (15 min) depressed the initial peak of the pressor response produced by carotid occlusion by 68% (15 ñ 1 vs 47 ñ 3 mmHg) and the mainteined rsponse by 52% (13 ñ 1 vs 27 ñ 4). Depression by chloralose was 48% (26 ñ 5 vs 50 ñ 3) and (19 ñ 2 vs 24 ñ 3), respectively. The inhibition progressively declined at 30, 60.90 and 120 min after pentobarbital but was unchanged up to 120 min after chloralose. 3. The baroreflex sensitivity index for bradycardic responses (phenylephrine injection) diminished by 50% after pentobarbital (-1.1 ñ 0.3 vs -2.2 ñ 0.3 beats/min per mmHg) and remained unaltered after chloralose. 4. The baroreflex sensitivity index for tachycardic responses (nitroprusside injection) was depressed by 61% after pentobarbital (-1.5 ñ 0.5 vs -3.8 - 0.5 beats/min per mmHg) and 35% after chloralose (-2.5 ñ 0.2 vs -3.9 ñ 0,5). 5. In general the depression of reflex control of ciruclation was more severe after pentobarbital than after chloralose anesthesia, while the resting control arterial pressurte was not affected by either. The inhibition of the baroreflex tachycardic responses was more intense than that of the bradycardic responses and represented a betther index of the depression exerted on the pressure responses to carotid occlusion

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

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

Measurements of renal sympathetic nerve activity in conscious sinoaortic denervated rats

The increase in renal sympathetic nerve activity (RSNA) produced in freely moving rats by sinoaortic denervation was analyzed both by couting the neural spikes and integrating the recorded electroneurogram. The percent increase was found to be greater when activity was calculated considering spike frequency (71%) rather than integrated voltage (54%). The different values obtained by the two methods suggests that after SAD, in addition to the increase in the nerve impulse frequency, there is an alteration in the pattern of nerve discharge