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.

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.

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.

Chronic intermittent hypoxia impairs diuretic and natriuretic responses to volume expansion in rats with preserved low-pressure baroreflex control of the kidney

2021 ◽  
Vol 320 (1) ◽  
pp. F1-F16
Author(s):  
Sara AlMarabeh ◽  
Julie O’Neill ◽  
Jeremy Cavers ◽  
Eric F. Lucking ◽  
Ken D. O’Halloran ◽  
...  
Keyword(s):  
High Pressure ◽  
Volume Expansion ◽  
Intermittent Hypoxia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Low Pressure ◽  
Chronic Intermittent Hypoxia ◽  
Transient Receptor Potential Vanilloid ◽  
Baroreflex Control ◽  
Obstructive Sleep

We examined the effects of exposure to chronic intermittent hypoxia (CIH) on baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory responses to volume expansion (VE) before and after intrarenal transient receptor potential vanilloid 1 (TRPV1) blockade by capsaizepine (CPZ). Male Wistar rats were exposed to 96 cycles of hypoxia per day for 14 days (CIH) or normoxia. Urine flow and absolute Na+ excretion during VE were less in CIH-exposed rats, but the progressive decrease in RSNA during VE was preserved. Assessment of the high-pressure baroreflex revealed an increase in the operating and response range of RSNA and decreased slope in CIH-exposed rats with substantial hypertension [+19 mmHg basal mean arterial pressure (MAP)] but not in a second cohort with modest hypertension (+12 mmHg). Intrarenal CPZ caused diuresis, natriuresis, and a reduction in MAP in sham-exposed (sham) and CIH-exposed rats. After intrarenal CPZ, diuretic and natriuretic responses to VE in CIH-exposed rats were equivalent to those of sham rats. TRPV1 expression in the renal pelvic wall was similar in both experimental groups. Exposure to CIH did not elicit glomerular hypertrophy, renal inflammation, or oxidative stress. We conclude that exposure to CIH 1) does not impair the low-pressure baroreflex control of RSNA; 2) has modest effects on the high-pressure baroreflex control of RSNA, most likely indirectly due to hypertension; 3) can elicit hypertension in the absence of kidney injury; and 4) impairs diuretic and natriuretic responses to fluid overload. Our results suggest that exposure to CIH causes renal dysfunction, which may be relevant to obstructive sleep apnea.

scholarly journals Effect of chronic intermittent hypoxia on noradrenergic activation of hypoglossal motoneurons

2012 ◽  
Vol 112 (2) ◽  
pp. 305-312 ◽  
Author(s):  
Georg M. Stettner ◽  
Victor B. Fenik ◽  
Leszek Kubin
Keyword(s):  
Intermittent Hypoxia ◽  
Upper Airway ◽  
Chronic Intermittent Hypoxia ◽  
Sprague Dawley ◽  
Excitatory Effect ◽  
Arterial Blood ◽  
Obstructive Sleep ◽  
Noradrenergic Innervation ◽  
Increased Sensitivity ◽  
S Period

In obstructive sleep apnea patients, elevated activity of the lingual muscles during wakefulness protects the upper airway against occlusions. A possibly related form of respiratory neuroplasticity is present in rats exposed to acute and chronic intermittent hypoxia (CIH). Since rats exposed to CIH have increased density of noradrenergic terminals and increased α1-adrenoceptor immunoreactivity in the hypoglossal (XII) nucleus, we investigated whether these anatomic indexes of increased noradrenergic innervation translate to increased sensitivity of XII motoneurons to noradrenergic activation. Adult male Sprague-Dawley rats were subjected to CIH for 35 days, with O2 level varying between 24% and 7% with 180-s period for 10 h/day. They were then anesthetized, vagotomized, paralyzed, and artificially ventilated. The dorsal medulla was exposed, and phenylephrine (2 mM, 10 nl) and then the α1-adrenoceptor antagonist prazosin (0.2 mM, 3 × 40 nl) were microinjected into the XII nucleus while XII nerve activity (XIIa) was recorded. The area under integrated XIIa was measured before and at different times after microinjections. The excitatory effect of phenylephrine on XII motoneurons was similar in sham- and CIH-treated rats. In contrast, spontaneous XIIa was more profoundly reduced following prazosin injections in CIH- than sham-treated rats [to 21 ± 7% (SE) vs. 40 ± 8% of baseline, P < 0.05] without significant changes in central respiratory rate, arterial blood pressure, or heart rate. Thus, consistent with increased neuroanatomic measures of noradrenergic innervation of XII motoneurons following exposure to CIH, prazosin injections revealed a stronger endogenous noradrenergic excitatory drive to XII motoneurons in CIH- than sham-treated anesthetized rats.

scholarly journals Intermittent Hypoxia-Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Esteban A. Moya ◽  
Paulina Arias ◽  
Carlos Varela ◽  
María P. Oyarce ◽  
Rodrigo Del Rio ◽  
...  
Keyword(s):  
Carotid Body ◽  
Reactive Nitrogen Species ◽  
Intermittent Hypoxia ◽  
Acute Hypoxia ◽  
Systemic Hypertension ◽  
Chronic Intermittent Hypoxia ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Obstructive Sleep

Oxidative stress is involved in the development of carotid body (CB) chemosensory potentiation and systemic hypertension induced by chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea. We tested whether peroxynitrite (ONOO−), a highly reactive nitrogen species, is involved in the enhanced CB oxygen chemosensitivity and the hypertension during CIH. Accordingly, we studied effects of Ebselen, an ONOO−scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir) in the CB, the CB chemosensory discharge, and arterial blood pressure (BP) in rats exposed to CIH. Male Sprague-Dawley rats were exposed to CIH (5% O2, 12 times/h, 8 h/day) for 7 days. Ebselen (10 mg/kg/day) was administrated using osmotic minipumps and BP measured with radiotelemetry. Compared to the sham animals, CIH-treated rats showed increased 3-NT-ir within the CB, enhanced CB chemosensory responses to hypoxia, increased BP response to acute hypoxia, and hypertension. Rats treated with Ebselen and exposed to CIH displayed a significant reduction in 3-NT-ir levels (60.8 ± 14.9 versus 22.9 ± 4.2 a.u.), reduced CB chemosensory response to 5% O2(266.5 ± 13.4 versus 168.6 ± 16.8 Hz), and decreased mean BP (116.9 ± 13.2 versus 82.1 ± 5.1 mmHg). Our results suggest that CIH-induced CB chemosensory potentiation and hypertension are critically dependent on ONOO−formation.

scholarly journals Reduced c-Fos expression in medullary catecholaminergic neurons in rats 20 h after exposure to chronic intermittent hypoxia

2013 ◽  
Vol 304 (7) ◽  
pp. R514-R522 ◽  
Author(s):  
Kate Benincasa Herr ◽  
Georg M. Stettner ◽  
Leszek Kubin
Keyword(s):  
Intermittent Hypoxia ◽  
Upper Airway ◽  
Chronic Intermittent Hypoxia ◽  
Motor Nucleus ◽  
Catecholaminergic Neurons ◽  
Arterial Blood ◽  
Baseline Activity ◽  
Obstructive Sleep ◽  
Catecholaminergic Transmission ◽  
Fos Expression

Persons affected by obstructive sleep apnea (OSA) have increased arterial blood pressure and elevated activity in upper airway muscles. Many cardiorespiratory features of OSA have been reproduced in rodents subjected to chronic-intermittent hypoxia (CIH). We previously reported that, following exposure to CIH, rats have increased noradrenergic terminal density in brain stem sensory and motor nuclei and upregulated expression of the excitatory α1-adrenergic receptors in the hypoglossal motor nucleus. This suggested that CIH may enhance central catecholaminergic transmission. We now quantified c-Fos expression in different groups of pontomedullary catecholaminergic neurons as an indirect way of assessing their baseline activity in rats subjected to CIH or sham treatment (7 AM-5 PM daily for 35 days). One day after the last CIH exposure, the rats were gently kept awake for 2.5 h and then were anesthetized and perfused, and their pontomedullary brain sections were subjected to dopamine β-hydroxylase (DBH) and c-Fos immunohistochemistry. DBH-positive cells were counted in the A1/C1, A2/C2, A5, subcoeruleus (sub-C) and A7 groups of catecholaminergic neurons, and the percentages of those expressing c-Fos were determined. We found that fewer DBH cells expressed c-Fos in CIH- than in sham-treated rats in the medulla (significant in the A1 group). In the pons (rostral A5, sub-C, and A7), c-Fos expression did not differ between the CIH- and sham-treated animals. We suggest that, when measured 20 h after the last CIH exposure, catecholaminergic transmission is enhanced through terminal sprouting and receptor upregulation rather than through increased baseline activity in pontomedullary catecholaminergic neurons.

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