Chronic intermittent hypoxia impairs baroreflex control of heart rate but enhances heart rate responses to vagal efferent stimulation in anesthetized mice

2007 ◽  
Vol 293 (2) ◽  
pp. H997-H1006 ◽  
Author(s):  
Min Lin ◽  
Rugao Liu ◽  
David Gozal ◽  
William B. Wead ◽  
Mark W. Chapleau ◽  
...  
Keyword(s):  
Heart Rate ◽  
Intermittent Hypoxia ◽  
Sympathetic Nerve Activity ◽  
Chronic Intermittent Hypoxia ◽  
Baroreflex Control ◽  
Low Frequencies ◽  
Arterial Blood ◽  
Different Doses ◽  
Left Vagus ◽  
Stimulation Of

Chronic intermittent hypoxia (CIH) leads to increased sympathetic nerve activity and arterial hypertension. In this study, we tested the hypothesis that CIH impairs baroreflex (BR) control of heart rate (HR) in mice, and that decreased cardiac chronotropic responsiveness to vagal efferent activity contributes to such impairment. C57BL/6J mice were exposed to either room air (RA) or CIH (6-min alternations of 21% O2 and 5.7% O2, 12 h/day) for 90 days. After the treatment period, mice were anesthetized (Avertin) and arterial blood pressure (ABP) was measured from the femoral artery. Mean ABP (MABP) was significantly increased in mice exposed to CIH (98.7 ± 2.5 vs. RA: 78.9 ± 1.4 mmHg, P < 0.001). CIH increased HR significantly (584.7 ± 8.9 beats/min; RA: 518.2 ± 17.9 beats/min, P < 0.05). Sustained infusion of phenylephrine (PE) at different doses (0.1–0.4 μg/min) significantly increased MABP in both CIH and RA mice, but the ABP-mediated decreases in HR were significantly attenuated in mice exposed to CIH ( P < 0.001). In contrast, decreases in HR in response to electrical stimulation of the left vagus nerve (30 μA, 2-ms pulses) were significantly enhanced in mice exposed to CIH compared with RA mice at low frequencies. We conclude that CIH elicits a sustained impairment of baroreflex control of HR in mice. The blunted BR-mediated bradycardia occurs despite enhanced cardiac chronotropic responsiveness to vagal efferent stimulation. This suggests that an afferent and/or a central defect is responsible for the baroreflex impairment following CIH.

scholarly journals Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguus of F344 rats

2009 ◽  
Vol 296 (2) ◽  
pp. R299-R308 ◽  
Author(s):  
Binbin Yan ◽  
Lihua Li ◽  
Scott W. Harden ◽  
David Gozal ◽  
Ying Lin ◽  
...  
Keyword(s):  
Heart Rate ◽  
Nmda Receptors ◽  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Intermittent Hypoxia ◽  
Area Postrema ◽  
Nucleus Ambiguus ◽  
Chronic Intermittent Hypoxia ◽  
Baroreflex Control ◽  
Arterial Blood

Chronic intermittent hypoxia (CIH), as occurs in sleep apnea, impairs baroreflex-mediated reductions in heart rate (HR) and enhances HR responses to electrical stimulation of vagal efferent. We tested the hypotheses that HR responses to activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-d-aspartate (NMDA) receptors in the nucleus ambiguus (NA) are reduced in CIH-exposed rats and that this impairment is associated with degeneration of glutamate receptor (GluR)-immunoreactive NA neurons. Fischer 344 rats (3–4 mo) were exposed to room air (RA) or CIH for 35–50 days ( n = 18/group). At the end of the exposures, AMPA (4 pmol, 20 nl) and NMDA (80 pmol, 20 nl) were microinjected into the same location of the left NA (−200 μm to +200 μm relative to caudal end of area postrema; n = 6/group), and HR and arterial blood pressure responses were measured. In addition, brain stem sections at the level of −800, −400, 0, +400, and +800 μm relative to obex were processed for AMPA and NMDA receptor immunohistochemistry. The number of NA neurons expressing AMPA receptors and NMDA receptors (NMDARs) was quantified. Compared with RA, we found that after CIH 1) HR responses to microinjection of AMPA into the left NA were reduced (RA −290 ± 30 vs. CIH −227 ± 15 beats/min, P < 0.05); 2) HR responses to microinjection of NMDA into the left NA were reduced (RA −302 ± 16 vs. CIH −238 ± 27 beats/min, P < 0.05); and 3) the number of NMDAR1, AMPA GluR1, and AMPA GluR2/3-immunoreactive cells in the NA was reduced ( P < 0.05). These results suggest that degeneration of NA neurons expressing GluRs contributes to impaired baroreflex control of HR in rats exposed to CIH.

Selective impairment of central mediation of baroreflex in anesthetized young adult Fischer 344 rats after chronic intermittent hypoxia

2007 ◽  
Vol 293 (5) ◽  
pp. H2809-H2818 ◽  
Author(s):  
He Gu ◽  
Min Lin ◽  
Jianyu Liu ◽  
David Gozal ◽  
Karie E. Scrogin ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Maximum Amplitude ◽  
Logistic Function ◽  
Stimulus Onset ◽  
Chronic Intermittent Hypoxia ◽  
Baroreflex Control ◽  
Maximum Slope ◽  
Peak Response ◽  
Fischer 344 ◽  
Arterial Blood

Baroreflex control of heart rate (HR) is impaired after chronic intermittent hypoxia (CIH). However, the location and nature of this response remain unclear. We examined baroreceptor afferent, vagal efferent, and central components of the baroreflex circuitry. Fischer 344 (F344) rats were exposed to room air (RA) or CIH for 35–50 days and were then anesthetized with isoflurane, ventilated, and catheterized for measurement of mean arterial blood pressure (MAP) and HR. Baroreceptor function was characterized by measuring percent changes of integrated aortic depressor nerve (ADN) activity (Int ADNA) relative to the baseline value in response to sodium nitroprusside- and phenylephrine-induced changes in MAP. Data were fitted to a sigmoid logistic function curve. HR responses to electrical stimulation of the left ADN and the right vagus nerve were assessed under ketamine-acepromazine anesthesia. Compared with RA controls, CIH significantly increased maximum baroreceptor gain or maximum slope, maximum Int ADNA, and Int ADNA range (maximum − minimum Int ADNA), whereas other parameters of the logistic function were unchanged. In addition, CIH increased the maximum amplitude of bradycardic response to vagal efferent stimulation and decreased the time from stimulus onset to peak response. In contrast, CIH significantly reduced the maximum amplitude of bradycardic response to left ADN stimulation and increased the time from stimulus onset to peak response. Therefore, CIH decreased central mediation of the baroreflex but augmented baroreceptor afferent function and vagal efferent control of HR.

Baroreflex control of muscle sympathetic nerve activity during skin surface cooling

2007 ◽  
Vol 103 (4) ◽  
pp. 1284-1289 ◽  
Author(s):  
Jian Cui ◽  
Sylvain Durand ◽  
Craig G. Crandall
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Blood Pressure ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Skin Surface ◽  
Surface Cooling ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Arterial Blood

Skin surface cooling improves orthostatic tolerance through a yet to be identified mechanism. One possibility is that skin surface cooling increases the gain of baroreflex control of efferent responses contributing to the maintenance of blood pressure. To test this hypothesis, muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate were recorded in nine healthy subjects during both normothermic and skin surface cooling conditions, while baroreflex control of MSNA and heart rate were assessed during rapid pharmacologically induced changes in arterial blood pressure. Skin surface cooling decreased mean skin temperature (34.9 ± 0.2 to 29.8 ± 0.6°C; P < 0.001) and increased mean arterial blood pressure (85 ± 2 to 93 ± 3 mmHg; P < 0.001) without changing MSNA ( P = 0.47) or heart rate ( P = 0.21). The slope of the relationship between MSNA and diastolic blood pressure during skin surface cooling (−3.54 ± 0.29 units·beat−1·mmHg−1) was not significantly different from normothermic conditions (−2.94 ± 0.21 units·beat−1·mmHg−1; P = 0.19). The slope depicting baroreflex control of heart rate was also not altered by skin surface cooling. However, skin surface cooling shifted the “operating point” of both baroreflex curves to high arterial blood pressures (i.e., rightward shift). Resetting baroreflex curves to higher pressure might contribute to the elevations in orthostatic tolerance associated with skin surface cooling.

Is baroreflex control of sympathetic activity and heart rate active in the preterm fetal sheep?

2009 ◽  
Vol 296 (3) ◽  
pp. R603-R609 ◽  
Author(s):  
Lindsea C. Booth ◽  
Simon C. Malpas ◽  
Carolyn J. Barrett ◽  
Sarah-Jane Guild ◽  
Alistair J. Gunn ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Pressure Control ◽  
Autonomic Response ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Fetal Sheep ◽  
Arterial Blood

The arterial baroreflex is a fundamental reflex that buffers rapid changes in arterial blood pressure (BP) via regulation of the heart rate and sympathetic nerve activity to the vasculature. In adults a sigmoidal relationship between BP and both heart rate and sympathetic nerve activity is well documented. Its role in blood pressure control before birth is unclear. Preterm babies have a high incidence of low BP, especially in the first few days of life, which could be related, in part, to immaturity of the baroreflex. In the present study, we investigated the baroreflex control of fetal heart rate and renal sympathetic nerve activity (RSNA) in preterm fetal sheep in utero (102 ± 1 days of gestation; term 140 days). Phenylephrine was associated with a significant increase in BP from 38 ± 2 to 58 ± 3 mmHg and a decrease in heart rate (HR) from 177 ± 4 to 116 ± 8 beats per minute (bpm). Sodium nitroprusside was associated with a significant fall in BP from 38 ± 2 to 26 ± 1 mmHg and an increase in HR from 182 ± 4 to 274 ± 8 bpm. However, the time between the 50% changes in BP and HR was significantly greater after hypotension than hypertension (31 ± 8 s vs. 14 ± 5 s, P < 0.05). No significant changes in RSNA occurred with either stimulus. This suggests that there are different maturational tempos for the components of the central autonomic response to altered blood pressure.

Aging and baroreflex control of RSNA and heart rate in rats

2000 ◽  
Vol 279 (5) ◽  
pp. R1865-R1871 ◽  
Author(s):  
M. C. Irigoyen ◽  
E. D. Moreira ◽  
A. Werner ◽  
F. Ida ◽  
M. D. Pires ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sympathetic Nerve Activity ◽  
Autonomic Control ◽  
Baroreflex Control ◽  
Renal Sympathetic Nerve Activity ◽  
Sympathetic Function ◽  
Arterial Blood ◽  
Reflex Bradycardia ◽  
Old Rats ◽  
Renal Sympathetic

Aging is associated with altered autonomic control of cardiovascular function, but baroreflex function in animal models of aging remains controversial. In this study, pressor and depressor agent-induced reflex bradycardia and tachycardia were attenuated in conscious old (24 mo) rats [57 and 59% of responses in young (10 wk) Wistar rats, respectively]. The intrinsic heart rate (HR, 339 ± 5 vs. 410 ± 10 beats/min) was reduced in aged animals, but no intergroup differences in resting mean arterial blood pressure (MAP, 112 ± 3 vs. 113 ± 5 mmHg) or HR (344 ± 9 vs. 347 ± 9 beats/min) existed between old and young rats, respectively. The aged group also exhibited a depressed (49%) parasympathetic contribution to the resting HR value (vagal effect) but preserved sympathetic function after intravenous methylatropine and propranolol. An implantable electrode revealed tonic renal sympathetic nerve activity (RSNA) was similar between groups. However, old rats showed impaired baroreflex control of HR and RSNA after intravenous nitroprusside (−0.63 ± 0.18 vs. −1.84 ± 0.4 bars · cycle−1 · mmHg−1 · s−1). Therefore, aging in rats is associated with 1) preserved baseline MAP, HR, and RSNA, 2) impaired baroreflex control of HR and RSNA, and 3) altered autonomic control of resting HR.

scholarly journals Chronic intermittent hypoxia in humans during 28 nights results in blood pressure elevation and increased muscle sympathetic nerve activity

2010 ◽  
Vol 299 (3) ◽  
pp. H925-H931 ◽  
Author(s):  
G. S. Gilmartin ◽  
M. Lynch ◽  
R. Tamisier ◽  
J. W. Weiss
Keyword(s):  
Blood Pressure ◽  
Sympathetic Nerve ◽  
Intermittent Hypoxia ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Chronic Intermittent Hypoxia ◽  
Sympathetic Activation ◽  
Nerve Activity ◽  
Blood Pressure Elevation ◽  
Healthy Humans

Chronic intermittent hypoxia (CIH) is thought to be responsible for the cardiovascular disease associated with obstructive sleep apnea (OSA). Increased sympathetic activation, altered vascular function, and inflammation are all putative mechanisms. We recently reported (Tamisier R, Gilmartin GS, Launois SH, Pepin JL, Nespoulet H, Thomas RJ, Levy P, Weiss JW. J Appl Physiol 107: 17–24, 2009) a new model of CIH in healthy humans that is associated with both increases in blood pressure and augmented peripheral chemosensitivity. We tested the hypothesis that exposure to CIH would also result in augmented muscle sympathetic nerve activity (MSNA) and altered vascular reactivity contributing to blood pressure elevation. We therefore exposed healthy subjects between the ages of 20 and 34 yr ( n = 7) to 9 h of nocturnal intermittent hypoxia for 28 consecutive nights. Cardiovascular and hemodynamic variables were recorded at three time points; MSNA was collected before and after exposure. Diastolic blood pressure (71 ± 1.3 vs. 74 ± 1.7 mmHg, P < 0.01), MSNA [9.94 ± 2.0 to 14.63 ± 1.5 bursts/min ( P < 0.05); 16.89 ± 3.2 to 26.97 ± 3.3 bursts/100 heartbeats (hb) ( P = 0.01)], and forearm vascular resistance (FVR) (35.3 ± 5.8 vs. 55.3 ± 6.5 mmHg·ml−1·min·100 g tissue, P = 0.01) all increased significantly after 4 wk of exposure. Forearm blood flow response following ischemia of 15 min (reactive hyperemia) fell below baseline values after 4 wk, following an initial increase after 2 wk of exposure. From these results we conclude that the increased blood pressure following prolonged exposure to CIH in healthy humans is associated with sympathetic activation and augmented FVR.

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