Abstract 477: Chronic Baroreflex Activation Improves Baroreflex Control of Heart Rate In Obesity

Impaired baroreflex control of heart rate (BRS) and attendant risk for cardiac arrhythmias are associated with sympathetically-mediated obesity hypertension. Since both global and renal-specific sympathoinhibition have sustained antihypertensive effects in obesity, we compared BRS in obese dogs subjected to 7 days of electrical baroreflex activation (BA) and, after recovery (REC), to bilateral surgical renal denervation (RDX). After control (C) measurements and 4 weeks of high fat diet, fat intake was reduced (RF) to maintain a body weight increase of ∼ 50%, which led to an increase in mean arterial pressure (MAP) from 100±2 to 117±3 mmHg and heart rate (HR) from 86±3 to 130±4 bpm. Obesity hypertension was associated with decreased sensitivity of 24h spontaneous BRS (determined by the sequence technique from daily beat-to-beat time series) and pulse interval (PI) variability (24h SD). While both BA and RDX abolished hypertension, only BA diminished tachycardia and normalized BRS, consequently improving HR variability. Short-term systolic blood pressure variability (5 min SD) also decreased with high fat feeding and was restored to control upon reduction of fat intake (RF) during established obesity hypertension, suggesting a vasoplegic effect of fat. These data suggest that in addition to the antihypertensive effects of sympathoinhibition, BA corrects cardiac baroreflex dysfunction in obesity hypertension, presumably by enhancing cardiac vagal activity. This in turn markedly improves depressed HR variability, a known risk factor for cardiac arrhythmic events.

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Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00464.2013 ◽

2013 ◽

Vol 305 (7) ◽

pp. H1080-H1088 ◽

Cited By ~ 28

Author(s):

Radu Iliescu ◽

Ionut Tudorancea ◽

Eric D. Irwin ◽

Thomas E. Lohmeier

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Arterial Pressure ◽

Cardiac Arrhythmias ◽

High Fat Diet ◽

Renal Denervation ◽

Gradual Increase ◽

High Fat ◽

Baroreflex Control ◽

Cardiovascular Dynamic

The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation—current therapies in patients with resistant hypertension, who are commonly obese—restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1–4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

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Loss of Diurnal Rhythms of Blood Pressure and Heart Rate Due to High Fat Feeding

American Journal of Hypertension ◽

10.1016/j.amjhyper.2005.04.015 ◽

2005 ◽

Vol 18 (10) ◽

pp. 1327-1328 ◽

Cited By ~ 1

Author(s):

R KANEDA ◽

K KARIO

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Diurnal Rhythms ◽

High Fat ◽

Fat Feeding

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Effects of aging on 24-h dynamic baroreceptor control of heart rate in ambulant subjects

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.4.h1606 ◽

1995 ◽

Vol 268 (4) ◽

pp. H1606-H1612 ◽

Cited By ~ 40

Author(s):

G. Parati ◽

A. Frattola ◽

M. Di Rienzo ◽

P. Castiglioni ◽

A. Pedotti ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Systolic Blood Pressure ◽

Baroreflex Sensitivity ◽

Regression Line ◽

Domain Analysis ◽

Pulse Interval ◽

Alpha Coefficient ◽

Baroreflex Control ◽

Effects Of Aging

The effects of aging on the dynamic modulation of baroreflex sensitivity over 24 h was assessed in eight elderly (mean age +/- SD, 63.9 +/- 3.2 yr) and in eight young (23.9 +/- 6.1 yr) mild or moderate essential hypertensive patients, who were subject to a 24-h intra-arterial (Oxford technique) blood pressure recording in ambulatory conditions. The sensitivity of baroreflex control of the heart rate was dynamically assessed by quantifying 1) the slope of the regression line between pulse interval (the reciprocal of heart rate) and systolic blood pressure changes over spontaneously occurring hypertension-bradycardia or hypotension-tachycardia sequences (time domain analysis) and 2) the ratio between spectral-powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha-coefficient: frequency domain analysis). The 24-h average sequence slope was lower in old than in young individuals (4.4 +/- 0.5 vs. 9.9 +/- 1.3 and 4.8 +/- 0.7 vs. 8.4 +/- 1.4 ms/mmHg for hypertension-bradycardia and hypotension-tachycardia sequences, respectively; P < 0.05 for both). Similar results were obtained by using the alpha-coefficient approach. The marked nighttime increase in baroreflex sensitivity observed in young individuals was much less evident in the elderly. Thus 24-h baroreflex sensitivity is markedly impaired by aging. The impairment becomes manifest also as an inability to increase baroreflex sensitivity at night.

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Bupivacaine Inhibits Baroreflex Control of Heart Rate in Conscious Rats

Anesthesiology ◽

10.1097/00000542-200001000-00032 ◽

2000 ◽

Vol 92 (1) ◽

pp. 197-197 ◽

Cited By ~ 5

Author(s):

Kyoung S. K. Chang ◽

Don R. Morrow ◽

Kazuyo Kuzume ◽

Michael C. Andresen

Keyword(s):

Heart Rate ◽

Baroreflex Sensitivity ◽

Cardiovascular Reflexes ◽

Pulse Interval ◽

Dependent Manner ◽

Baroreflex Control ◽

Conscious Rats ◽

Reflex Bradycardia ◽

Adrenergic Antagonist ◽

Dose Dependent

Background Because exposure to intravenously administered bupivacaine may alter cardiovascular reflexes, the authors examined bupivacaine actions on baroreflex control of heart rate in conscious rats. Methods Baroreflex sensitivity (pulse interval vs. systolic blood pressure in ms/mmHg) was determined before, and 1.5 and 15.0 min after rapid intravenous administration of bupivacaine (0.5, 1.0, and 2.0 mg/kg) using heart rate changes evoked by intravenously administered phenylephrine or nitroprusside. The actions on the sympathetic and parasympathetic autonomic divisions of the baroreflex were tested in the presence of a muscarinic antagonist methyl atropine and a beta-adrenergic antagonist atenolol. Results Within seconds of injection of bupivacaine, mean arterial pressure increased and heart rate decreased in a dose-dependent manner. Baroreflex sensitivity was unaltered after administration of 0.5 mg/kg bupivacaine. In addition, 1 mg/kg bupivacaine at 1.5 min depressed phenylephrine-evoked reflex bradycardia (0.776 +/- 0.325 vs. 0.543 +/- 0.282 ms/mmHg, P < 0.05) but had no effect on nitroprusside-induced tachycardia. Bupivacaine (2 mg/kg), however, depressed reflex bradycardia and tachycardia (phenylephrine, 0.751 +/- 0.318 vs. 0.451 +/- 0.265; nitroprusside, 0.839 +/- 0.256 vs. 0.564 +/- 0.19 ms/mmHg, P < 0.05). Baroreflex sensitivity returned to prebupivacaine levels by 15 min. Bupivacaine (2 mg/kg), in the presence of atenolol, depressed baroreflex sensitivity (phenylephrine, 0.633 +/- 0.204 vs. 0.277 +/- 0.282; nitroprusside, 0.653 +/- 0.142 vs. 0.320 +/- 0.299 ms/mmHg, P < 0.05). In contrast, bupivacaine did not alter baroreflex sensitivity in the presence of methyl atropine. Conclusions Bupivacaine, in clinically relevant concentrations, inhibits baroreflex control of heart rate in conscious rats. This inhibition appears to involve primarily vagal components of the baroreflex-heart rate pathways.

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DIURNAL PATTERNS OF HEART RATE AND BLOOD PRESSURE DURING HIGH FAT FEEDING AND HYDRALAZINE TREATMENT

Medicine & Science in Sports & Exercise ◽

10.1097/00005768-200305001-01538 ◽

2003 ◽

Vol 35 (Supplement 1) ◽

pp. S277

Author(s):

J W. King ◽

J S. Cohen ◽

J F. Carroll

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

High Fat ◽

Diurnal Patterns ◽

Fat Feeding

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High-fat feeding alters both basal and stress-induced hypothalamic-pituitary-adrenal activity in the rat

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1997.273.6.e1168 ◽

1997 ◽

Vol 273 (6) ◽

pp. E1168-E1177 ◽

Cited By ~ 43

Author(s):

Beth M. Tannenbaum ◽

David N. Brindley ◽

Gloria S. Tannenbaum ◽

Mary F. Dallman ◽

M. Dawn McArthur ◽

...

Keyword(s):

Hpa Axis ◽

Dietary Fat ◽

High Fat Diet ◽

Male Rats ◽

Fat Intake ◽

High Fat ◽

Hypothalamic Pituitary Adrenal ◽

Resistance To Insulin ◽

Artery Disease ◽

Fat Feeding

High-fat feeding induces insulin resistance and increases the risk for the development of diabetes and coronary artery disease. Glucocorticoids exacerbate this hyperinsulinemic state, rendering an individual at further risk for chronic disease. The present studies were undertaken to determine whether dietary fat-induced increases in corticosterone (B) reflect alterations in the regulatory components of the hypothalamic-pituitary-adrenal (HPA) axis. Adult male rats were maintained on a high-fat (20%) or control (4%) diet for varying periods of time. Marked elevations in light-phase spontaneous basal B levels were evident as early as 7 days after fat diet onset, and B concentrations remained significantly elevated up to 21 days after fat diet onset compared with controls. In contrast, there were no significant effects on any parameters of spontaneous growth hormone secretory profiles, thus providing support for the specificity of the effects on the HPA axis. In a second study, all groups of rats fed the high-fat diet for 1, 9, or 12 wk exhibited significantly elevated levels of plasma adrenocorticotropic hormone, B, fatty acid, and glucose before, during, and/or at 20, 60, and/or 120 min after the termination of a restraint stress. Furthermore, 12-wk fat-fed animals showed a significant resistance to insulin compared with normally fed controls. There were no differences in negative feedback efficacy in high-fat-fed rats vs. controls. Taken together, these results suggest that dietary fat intake acts as a background form of chronic stress, elevating basal B levels and enhancing HPA responses to stress.

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Baroreflex control of heart rate in humans during nitroprusside-induced hypotension

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1982.243.1.r18 ◽

1982 ◽

Vol 243 (1) ◽

pp. R18-R24 ◽

Cited By ~ 3

Author(s):

R. Y. Chen ◽

F. C. Fan ◽

G. B. Schuessler ◽

S. Chien

Keyword(s):

Heart Rate ◽

Arterial Pressure ◽

Sympathetic Activity ◽

Time Lag ◽

Systolic Pressure ◽

Initial Slope ◽

Pulse Interval ◽

Halothane Anesthesia ◽

Baroreflex Control ◽

Induced Hypotension

The baroreflex control of heart rate was investigated on 10 informed human subjects during light halothane anesthesia (0.3-0.5%, inspired concentration). The relationship of systolic pressure (SP) to the succeeding pulse interval (PI) was evaluated on a beat-to-beat basis during the entire course of sodium nitroprusside (SNP) depressor test. The initial slope of SP-PI plot (dPI/dSP) was used as an index of the sensitivity of baroreflex control of heart rate. Following an injection of SNP (4-6 micrograms/kg), dPI/dt was related directly to dPI/dSP, whereas the latter was inversely correlated with dSP/dt. The recovery of PI lagged behind that of SP, and there was a hysteresislike loop on the SP-PI plot. The time lag of PI recovery and the loop of SP-PI plot were markedly decreased by propranolol treatment and significantly increased by atropine. The slopes of SP-PI plot were significantly decreased by atropine but relatively unaffected by propranolol. These results indicate that SNP-induced hypotension in man during halothane anesthesia is associated with a withdrawal of parasympathetic inhibition and an enhancement of sympathetic activity. The autonomic control of heart rate in response to rapid changes in arterial pressure induced by SNP is dominated by parasympathetic influence; the more persistent sympathetic activity only becomes evident when the parasympathetic influence subsides quickly as the arterial pressure stays relatively constant at a new level. The slope of SP-PI plot (dPI/dSP) and the ratio of dPI/dt to dSP/dt during the decreasing pressure phase of SNP test can be used as indices for the sensitivity of baroreflex control of heart rate.

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