scholarly journals Chronic Intermittent Hypoxia Induces Systemic Hypertension, and Tachycardia, and Impairs Baroreflex Control of the Heart Rate in Conscious Mice (C57BL/6J)

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Min Lin ◽  
H. Gu ◽  
D. Gozal ◽  
R. Liu
Keyword(s):  
Heart Rate ◽  
Intermittent Hypoxia ◽  
Systemic Hypertension ◽  
Chronic Intermittent Hypoxia ◽  
Baroreflex Control

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.

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.

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 Maladaptive Pulmonary Vascular Responses to Chronic Sustained and Chronic Intermittent Hypoxia in Rat

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 54
Author(s):  
Jesus Prieto-Lloret ◽  
Elena Olea ◽  
Ana Gordillo-Cano ◽  
Inmaculada Docio ◽  
Ana Obeso ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Carotid Body ◽  
Pulmonary Circulation ◽  
Intermittent Hypoxia ◽  
Pulmonary Arteries ◽  
Systemic Circulation ◽  
Systemic Hypertension ◽  
Chronic Intermittent Hypoxia ◽  
Respiratory Disorder ◽  
Obstructive Sleep

Chronic sustained hypoxia (CSH), as found in individuals living at a high altitude or in patients suffering respiratory disorders, initiates physiological adaptations such as carotid body stimulation to maintain oxygen levels, but has deleterious effects such as pulmonary hypertension (PH). Obstructive sleep apnea (OSA), a respiratory disorder of increasing prevalence, is characterized by a situation of chronic intermittent hypoxia (CIH). OSA is associated with the development of systemic hypertension and cardiovascular pathologies, due to carotid body and sympathetic overactivation. There is growing evidence that CIH can also compromise the pulmonary circulation, causing pulmonary hypertension in OSA patients and animal models. The aim of this work was to compare hemodynamics, vascular contractility, and L-arginine-NO metabolism in two models of PH in rats, associated with CSH and CIH exposure. We demonstrate that whereas CSH and CIH cause several common effects such as an increased hematocrit, weight loss, and an increase in pulmonary artery pressure (PAP), compared to CIH, CSH seems to have more of an effect on the pulmonary circulation, whereas the effects of CIH are apparently more targeted on the systemic circulation. The results suggest that the endothelial dysfunction evident in pulmonary arteries with both hypoxia protocols are not due to an increase in methylated arginines in these arteries, although an increase in plasma SDMA could contribute to the apparent loss of basal NO-dependent vasodilation and, therefore, the increase in PAP that results from CIH.

scholarly journals Chronic intermittent hypoxia-hypercapnia blunts heart rate responses and alters neurotransmission to cardiac vagal neurons

2014 ◽  
Vol 592 (13) ◽  
pp. 2799-2811 ◽  
Author(s):  
Jhansi Dyavanapalli ◽  
Heather Jameson ◽  
Olga Dergacheva ◽  
Vivek Jain ◽  
Mona Alhusayyen ◽  
...  
Keyword(s):  
Heart Rate ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia

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.

Dynamic time-varying analysis of heart rate and blood pressure variability in cats exposed to short-term chronic intermittent hypoxia

2008 ◽  
Vol 295 (1) ◽  
pp. R28-R37 ◽  
Author(s):  
Sergio Rey ◽  
Mika P. Tarvainen ◽  
Pasi A. Karjalainen ◽  
Rodrigo Iturriaga
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Intermittent Hypoxia ◽  
Acute Hypoxia ◽  
Low Frequency ◽  
Dynamic Responses ◽  
Chronic Intermittent Hypoxia ◽  
Short Term ◽  
Obstructive Sleep ◽  
Induced Hypertension

Chronic intermittent hypoxia (CIH) contributes to the development of hypertension in patients with obstructive sleep apnea and animal models. However, the early cardiovascular changes that precede CIH-induced hypertension are not completely understood. Nevertheless, it has been proposed that one of the possible contributing mechanisms to CIH-induced hypertension is a potentiation of carotid body (CB) hypoxic chemoreflexes. Therefore, we studied the dynamic responses of heart rate, blood pressure, and their variabilities during acute exposure to different levels of hypoxia after CIH short-term preconditioning (4 days) in cats. In addition, we measured baroreflex sensitivity (BRS) on the control of heart rate by noninvasive techniques. To assess the relationships among these indexes and CB chemoreflexes, we also recorded CB chemosensory discharges. Our data show that short-term CIH reduced BRS, potentiated the increase in heart rate induced by acute hypoxia, and was associated with a dynamic shift of heart rate variability (HRV) spectral indexes toward the low-frequency band. In addition, we found a striking linear correlation ( r = 0.97) between the low-to-high frequency ratio of HRV and baseline. CB chemosensory discharges in the CIH-treated cats. Thus, our results suggest that cyclic hypoxic stimulation of the CB by short-term CIH induces subtle but clear selective alterations of HRV and BRS in normotensive cats.

Sign in / Sign up

Export Citation Format

Share Document