Chronic intermittent hypoxia alters NE reactivity and mechanics of skeletal muscle resistance arteries

2006 ◽  
Vol 100 (4) ◽  
pp. 1117-1123 ◽  
Author(s):  
Shane A. Phillips ◽  
E. B. Olson ◽  
Julian H. Lombard ◽  
Barbara J. Morgan
Keyword(s):  
Skeletal Muscle ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Physiological Salt Solution ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Sprague Dawley Rats ◽  
Resting Tone ◽  
Wall Distensibility

Although arterial dilator reactivity is severely impaired during exposure of animals to chronic intermittent hypoxia (CIH), few studies have characterized vasoconstrictor responsiveness in resistance arteries of this model of sleep-disordered breathing. Sprague-Dawley rats were exposed to CIH (10% inspired O2 fraction for 1 min at 4-min intervals; 12 h/day) for 14 days. Control rats were housed under normoxic conditions. Diameters of isolated gracilis muscle resistance arteries (GA; 120–150 μm) were measured by television microscopy before and during exposure to norepinephrine (NE) and angiotensin II (ANG II) and at various intraluminal pressures between 20 and 140 mmHg in normal and Ca2+-free physiological salt solution. There was no difference in the ability of GA to constrict in response to ANG II ( P = 0.42; not significant; 10−10–10−7 M). However, resting tone, myogenic activation, and vasoconstrictor responses to NE ( P < 0.001; 10−9–10−6 M) were reduced in CIH vs. controls. Treatment of rats with the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol; 1 mM) in the drinking water restored myogenic responses and NE-induced constrictions of CIH rats, suggesting that elevated superoxide production during exposure to CIH attenuates vasoconstrictor responsiveness to NE and myogenic activation in skeletal muscle resistance arteries. CIH also leads to an increased stiffness and reduced vessel wall distensibility that were not correctable with oral tempol treatment.

Chronic intermittent hypoxia impairs endothelium-dependent dilation in rat cerebral and skeletal muscle resistance arteries

2004 ◽  
Vol 286 (1) ◽  
pp. H388-H393 ◽  
Author(s):  
Shane A. Phillips ◽  
E. B. Olson ◽  
Barbara J. Morgan ◽  
Julian H. Lombard
Keyword(s):  
Skeletal Muscle ◽  
Intermittent Hypoxia ◽  
Acute Hypoxia ◽  
Cerebral Arteries ◽  
Chronic Intermittent Hypoxia ◽  
Physiological Salt Solution ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Before And After ◽  
Fraction Of Inspired Oxygen

The goal of the present study was to evaluate the effects of relatively short-term chronic intermittent hypoxia (CIH) on endothelial function of resistance vessels in the skeletal muscle and cerebral circulations. Sprague-Dawley rats were exposed to 14 days of CIH (10% fraction of inspired oxygen for 1 min at 4-min intervals, 12 h/day, n = 6). Control rats ( n = 6) were housed under normoxic conditions. After 14 days, resistance arteries of the gracilis muscle (GA) and middle cerebral arteries (MCA) were isolated and cannulated with micropipettes, perfused and superfused with physiological salt solution, and equilibrated with 21% O2-5% CO2 in a heated chamber. The arteries were pressurized to 90 mmHg, and vessel diameters were measured via a video micrometer before and after exposure to ACh (10–7–10–4 M), sodium nitroprusside (10–6 M), and acute reduction of Po2 in the perfusate/superfusate (from 140 to 40 mmHg). ACh-induced dilations of GA and MCA from animals exposed to CIH were greatly attenuated, whereas responses to nitroprusside were similar to controls. Dilations of both GA and MCA in response to acute reductions in Po2 were virtually abolished in animals exposed to CIH compared with controls. These findings suggest that exposure to CIH reduces the bioavailability of nitric oxide in the cerebral and skeletal muscle circulations and severely blunts vasodilator responsiveness to acute hypoxia.

scholarly journals AT1a dependent GABAA inhibition in the MnPO following chronic intermittent hypoxia

2021 ◽  
Author(s):  
George E. Farmer ◽  
Joel T. Little ◽  
Alexandria B. Marciante ◽  
J. Thomas Cunningham
Keyword(s):  
Intermittent Hypoxia ◽  
Receptor Expression ◽  
Chronic Intermittent Hypoxia ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Spontaneous Action ◽  
Potential Activity ◽  
At1a Receptor

Chronic intermittent hypoxia (CIH) is associated with diurnal hypertension, increased sympathetic nerve activity (SNA), and increases in circulating angiotensin II (ANG II). In rats, CIH increases angiotensin type 1 (AT1a) receptor expression in the median preoptic nucleus (MnPO), and pharmacological blockade or viral knockdown of this receptor prevents CIH dependent increases in diurnal blood pressure. The current study investigates the role of AT1a receptor in modulating the activity of MnPO neurons following 7 days of CIH. Male Sprague-Dawley rats received MnPO injections of an adeno-associated virus with a shRNA against the AT1a receptor or a scrambled control. Rats were then exposed to CIH 8 h a day for 7 days. In vitro loose patch recordings of spontaneous action potential activity were made from labeled MnPO neurons in response to brief focal application of ANG II or the GABAA receptor agonist muscimol. Additionally, MnPO KCC2 protein expression was assessed using Western blot. CIH impaired the duration but not the magnitude of ANG II mediated excitation in the MnPO. Both CIH and AT1a knockdown also impaired GABAA mediated inhibition and CIH with AT1a knockdown produced GABAA mediated excitation. Recordings using the ratiometric Cl- indicator ClopHensorN showed CIH was associated with Cl- efflux in MnPO neurons that was associated with decreased KCC2 phosphorylation. The combination of CIH and AT1a knockdown attenuated reduced KCC2 phosphorylation seen with CIH alone. The current study shows that CIH, through the activity of AT1a receptors, can impair GABAA mediated inhibition in the MnPO contributing sustained hypertension.

20-HETE Contributes to Myogenic Activation of Skeletal Muscle Resistance Arteries in Brown Norway and Sprague-Dawley Rats

2001 ◽  
Vol 8 (1) ◽  
pp. 45-55
Author(s):  
JEFFERSON C. FRISBEE ◽  
RICHARD J. ROMAN ◽  
JOHN R. FALCK ◽  
U. MURALI KRISHNA ◽  
JULIAN H. LOMBARD
Keyword(s):  
Skeletal Muscle ◽  
Brown Norway ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Sprague Dawley Rats

Elevated salt intake impairs dilation of rat skeletal muscle resistance arteries via ANG II suppression

2000 ◽  
Vol 278 (2) ◽  
pp. H500-H506 ◽  
Author(s):  
David S. Weber ◽  
Julian H. Lombard
Keyword(s):  
Salt Intake ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Dietary Salt ◽  
Short Term ◽  
Dietary Salt Intake ◽  
Sprague Dawley Rats ◽  
Camp And Cgmp ◽  
Prostacyclin Analog

Vasodilator responses were assessed in resistance arteries (100–200 μm) isolated from the gracilis muscle of normotensive rats after changes in dietary salt intake. Sprague-Dawley rats were maintained on either a high-salt (HS) diet (4.0% NaCl) or a low-salt (LS) diet (0.4% NaCl) for 4–8 wk (chronic) or 3 days (short-term) with water ad libitum. One group of short-term HS rats received a continuous intravenous infusion of a low dose (5 ng ⋅ kg− 1 ⋅ min− 1) of ANG II to prevent the ANG II suppression that occurs with HS diet. Short-term and chronic HS diet eliminated arterial dilation in response to ACh and reduced[Formula: see text] (30–40 mmHg) and the stable prostacyclin analog iloprost. ANG II infusion preserved the response to these vasodilator stimuli in short-term HS animals. Dilator responses to sodium nitroprusside and forskolin were unaffected by HS diet. These findings suggest that ANG II suppression during HS diet impairs vascular relaxation mechanisms upstream from the cAMP and cGMP second messenger systems.

20-HETE Contributes to Myogenic Activation of Skeletal Muscle Resistance Arteries in Brown Norway and Sprague–Dawley Rats

2001 ◽  
Vol 8 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Jefferson C Frisbee ◽  
Richard J Roman ◽  
John R Falck ◽  
U Murali Krishna ◽  
Julian H Lombard
Keyword(s):  
Skeletal Muscle ◽  
Brown Norway ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Sprague Dawley 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 Chronic intermittent hypoxia increases blood pressure and expression of FosB/ΔFosB in central autonomic regions

2011 ◽  
Vol 301 (1) ◽  
pp. R131-R139 ◽  
Author(s):  
W. David Knight ◽  
Joel T. Little ◽  
Flavia R. Carreno ◽  
Glenn M. Toney ◽  
Steven W. Mifflin ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Renin Angiotensin System ◽  
Brain Regions ◽  
Ventrolateral Medulla ◽  
Chronic Intermittent Hypoxia ◽  
Preoptic Nucleus ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Sprague Dawley Rats ◽  
Obstructive Sleep

Chronic intermittent hypoxia (CIH) models repetitive bouts of arterial hypoxemia that occur in humans suffering from obstructive sleep apnea. CIH has been linked to persistent activation of arterial chemoreceptors and the renin-angiotensin system, which have been linked to chronic elevations of sympathetic nerve activity (SNA) and mean arterial pressure (MAP). Because Fos and FosB are transcription factors involved in activator protein (AP)-1 driven central nervous system neuronal adaptations, this study determined if CIH causes increased Fos or FosB staining in brain regions that regulate SNA and autonomic function. Male Sprague Dawley rats were instrumented with telemetry transmitters for continuous recording of MAP and heart rate (HR). Rats were exposed to continuous normoxia (CON) or to CIH for 8 h/day for 7 days. CIH increased MAP by 7–10 mmHg without persistently affecting HR. A separate group of rats was killed 1 day after 7 days of CIH for immunohistochemistry. CIH did not increase Fos staining in any brain region examined. Staining for FosB/ΔFosB was increased in the organum vasculosum of the lamina terminalis (CON: 9 ± 1; CIH: 34 ± 3 cells/section), subfornical organ (CON: 7 ± 2; CIH: 31 ± 3), median preoptic nucleus (CON 15 ± 1; CIH: 38 ± 3), nucleus of the solitary tract (CON: 9 ± 2; CIH: 28 ± 4), A5 (CON: 3 ± 1; CIH: 10 ± 1), and rostral ventrolateral medulla (CON: 5 ± 1; CIH: 17 ± 2). In the paraventricular nucleus, FosB/ΔFosB staining was located mainly in the dorsal and medial parvocellular subnuclei. CIH did not increase FosB/ΔFosB staining in caudal ventrolateral medulla or supraoptic nucleus. These data indicate that CIH induces an increase in FosB/ΔFosB in autonomic nuclei and suggest that AP-1 transcriptional regulation may contribute to stable adaptive changes that support chronically elevated SNA.

High-salt diet impairs hypoxia-induced cAMP production and hyperpolarization in rat skeletal muscle arteries

2001 ◽  
Vol 281 (4) ◽  
pp. H1808-H1815 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
Francis A. Sylvester ◽  
Julian H. Lombard
Keyword(s):  
Skeletal Muscle ◽  
Cholera Toxin ◽  
High Salt ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
High Salt Diet ◽  
Sprague Dawley Rats ◽  
Prostaglandin H ◽  
Camp Levels

This study determined the effects of hypoxia on diameter, vascular smooth muscle (VSM) transmembrane potential ( E m), and vascular cAMP levels for in vitro cannulated skeletal muscle resistance arteries (gracilis arteries) from Sprague-Dawley rats fed a low-salt (LS) or a high-salt (HS) diet. Arterial diameter and VSM E m were measured in response to hypoxia, iloprost, cholera toxin, forskolin, and aprikalim. In HS rats, arterial dilation and VSM hyperpolarization after hypoxia, iloprost, and cholera toxin were impaired versus responses in LS rats, whereas responses to forskolin and aprikalim were unaltered. Blockade of prostaglandin H2 and thromboxane A2 receptors had no effect on responses to hypoxia or iloprost in vessels from both rat groups, suggesting that inappropriate activation of these receptors does not contribute to the impaired hypoxic dilation with HS. Hypoxia, cholera toxin, and iloprost increased vascular cAMP levels in vessels of LS rats only, whereas forskolin increased cAMP levels in all vessels. These data suggest that reduced hypoxic dilation of skeletal muscle microvessels in rats on a HS diet may reflect an impaired ability of VSM to produce cAMP after exposure to prostacyclin.

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