scholarly journals Chronic hypoxia abolishes posthypoxia frequency decline in the anesthetized rat

2003 ◽  
Vol 285 (6) ◽  
pp. R1322-R1330 ◽  
Author(s):  
Oleg Ilyinsky ◽  
Gleb Tolstykh ◽  
Steve Mifflin
Keyword(s):  
Phrenic Nerve ◽  
Chronic Hypoxia ◽  
Acute Hypoxia ◽  
Sprague Dawley ◽  
Burst Frequency ◽  
Anesthetized Rats ◽  
Sprague Dawley Rats ◽  
Bilateral Carotid ◽  
Central Network ◽  
Nerve Discharge

In anesthetized rats, increases in phrenic nerve amplitude and frequency during brief periods of hypoxia are followed by a reduction in phrenic nerve burst frequency [posthypoxia frequency decline (PHFD)]. We investigated the effects of chronic exposure to hypoxia on PHFD and on peripheral and central O2-sensing mechanisms. In Inactin-anesthetized (100 mg/kg) Sprague-Dawley rats, phrenic nerve discharge and arterial pressure responses to 10 s N2 inhalation were recorded after exposure to hypoxia (10 ± 0.5% O2) for 6-14 days. Compared with rats maintained at normoxia, PHFD was abolished in chronic hypoxic rats. Because of inhibition of PHFD, the increased phrenic burst frequency and amplitude after N2 inhalation persisted for 1.8-2.8 times longer in chronic hypoxic (70 s) compared with normoxic (25-40 s) rats ( P < 0.05). After acute bilateral carotid body denervation, N2 inhalation produced a short depression of phrenic nerve discharge in both chronic hypoxic and normoxic rats. However, the degree and duration of depression of phrenic nerve discharge was smaller in chronic hypoxic compared with normoxic rats ( P < 0.05). We conclude that after exposure to chronic hypoxia, a reduction in PHFD contributes to an increased duration of the acute hypoxic ventilatory response in anesthetized rats. Furthermore, after exposure to chronic hypoxia, the central network responsible for respiration is more resistant to the depressant effects of acute hypoxia in anesthetized rats.

scholarly journals Periodicity During Hypercapnic and Hypoxic Stimulus Is Crucial in Distinct Aspects of Phrenic Nerve Plasticity

2016 ◽  
pp. 133-143 ◽  
Author(s):  
I. STIPICA ◽  
I. PAVLINAC DODIG ◽  
R. PECOTIC ◽  
Z. DOGAS ◽  
Z. VALIC ◽  
...  
Keyword(s):  
Phrenic Nerve ◽  
Sprague Dawley ◽  
Long Term Effects ◽  
Burst Frequency ◽  
Mechanically Ventilated ◽  
Sprague Dawley Rats ◽  
Pattern Sensitivity ◽  
Long Term Facilitation ◽  
Nerve Plasticity

This study was undertaken to determine pattern sensitivity of phrenic nerve plasticity in respect to different respiratory challenges. We compared long-term effects of intermittent and continuous hypercapnic and hypoxic stimuli, and combined intermittent hypercapnia and hypoxia on phrenic nerve plasticity. Adult, male, urethane-anesthetized, vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats were exposed to: acute intermittent hypercapnia (AIHc or AIHcO2), acute intermittent hypoxia (AIH), combined intermittent hypercapnia and hypoxia (AIHcH), continuous hypercapnia (CHc), or continuous hypoxia (CH). Peak phrenic nerve activity (pPNA) and burst frequency were analyzed during baseline (T0), hypercapnia or hypoxia exposures, at 15, 30, and 60 min (T60) after the end of the stimulus. Exposure to acute intermittent hypercapnia elicited decrease of phrenic nerve frequency from 44.25±4.06 at T0 to 35.29±5.21 at T60, (P=0.038, AIHc) and from 45.5±2.62 to 37.17±3.68 breaths/min (P=0.049, AIHcO2), i.e. frequency phrenic long term depression was induced. Exposure to AIH elicited increase of pPNA at T60 by 141.0±28.2 % compared to baseline (P=0.015), i.e. phrenic long-term facilitation was induced. Exposure to AIHcH, CHc, or CH protocols failed to induce long-term plasticity of the phrenic nerve. Thus, we conclude that intermittency of the hypercapnic or hypoxic stimuli is needed to evoke phrenic nerve plasticity.

scholarly journals Chronic intermittent hypoxia alters ventilatory and metabolic responses to acute hypoxia in rats

2016 ◽  
Vol 120 (10) ◽  
pp. 1186-1195 ◽  
Author(s):  
Barbara J. Morgan ◽  
Russell Adrian ◽  
Zun-yi Wang ◽  
Melissa L. Bates ◽  
John M. Dopp
Keyword(s):  
Intermittent Hypoxia ◽  
Acute Hypoxia ◽  
Sprague Dawley ◽  
Glomus Cell ◽  
Stimulus Response ◽  
Sprague Dawley Rats ◽  
Ventilatory Equivalent ◽  
Before And After ◽  
Conscious Animals ◽  
Carotid Body Glomus Cells

We determined the effects of chronic exposure to intermittent hypoxia (CIH) on chemoreflex control of ventilation in conscious animals. Adult male Sprague-Dawley rats were exposed to CIH [nadir oxygen saturation (SpO2), 75%; 15 events/h; 10 h/day] or normoxia (NORM) for 21 days. We assessed the following responses to acute, graded hypoxia before and after exposures: ventilation (V̇e, via barometric plethysmography), V̇o2 and V̇co2 (analysis of expired air), heart rate (HR), and SpO2 (pulse oximetry via neck collar). We quantified hypoxia-induced chemoreceptor sensitivity by calculating the stimulus-response relationship between SpO2 and the ventilatory equivalent for V̇co2 (linear regression). An additional aim was to determine whether CIH causes proliferation of carotid body glomus cells (using bromodeoxyuridine). CIH exposure increased the slope of the V̇e/V̇co2/SpO2 relationship and caused hyperventilation in normoxia. Bromodeoxyuridine staining was comparable in CIH and NORM. Thus our CIH paradigm augmented hypoxic chemosensitivity without causing glomus cell proliferation.

scholarly journals Selected Contribution: Phrenic long-term facilitation requires 5-HT receptor activation during but not following episodic hypoxia

2001 ◽  
Vol 90 (5) ◽  
pp. 2001-2006 ◽  
Author(s):  
D. D. Fuller ◽  
A. G. Zabka ◽  
T. L. Baker ◽  
G. S. Mitchell
Keyword(s):  
Receptor Antagonist ◽  
Phrenic Nerve ◽  
Receptor Activation ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Sprague Dawley Rats ◽  
Episodic Hypoxia ◽  
Baseline Levels ◽  
Long Term Facilitation

Episodic hypoxia evokes a sustained augmentation of respiratory motor output known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the hypothesis that 5-HT receptor activation is necessary for the induction but not maintenance of phrenic LTF. Peak integrated phrenic nerve activity (∫Phr) was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial Po 2 = 40 ± 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats [ 1) control ( n = 11), 2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45 min after episodic hypoxia ( n = 7 each)]. Ketanserin transiently decreased ∫Phr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, ∫Phr was significantly elevated from baseline in control and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is necessary to initiate (during hypoxia) but not maintain (following hypoxia) phrenic LTF.

Long-term captopril treatment restores natriuresis after carotid baroreceptor activation in the SHR

1997 ◽  
Vol 273 (1) ◽  
pp. R70-R79
Author(s):  
J. P. Valentin ◽  
S. A. Mazbar ◽  
M. H. Humphreys
Keyword(s):  
Renal Plasma Flow ◽  
Renal Nerves ◽  
Sprague Dawley ◽  
Wky Rats ◽  
Sprague Dawley Rats ◽  
Long Term Treatment ◽  
Bilateral Carotid ◽  
Wistar Kyoto ◽  
Captopril Treatment

In anesthetized Sprague-Dawley rats, intermittent bilateral carotid artery traction (BilCAT) caused a transient decrease in mean arterial pressure (MAP) of 28 +/- 3 mmHg and led to a progressive increase in sodium excretion (UNaV) that nearly doubled 45-90 min after initiation of the repetitive application of BilCAT (P < 0.001). This natriuresis was accompanied by an increase in glomerular filtration rate (GFR) from 2.70 +/- 0.3 to 3.2 +/- 0.3 ml/min (P < 0.001), no change in renal plasma flow [clearance of p-aminohippurate (PAH)], and an increase in the fractional excretion of lithium. Rats with bilateral renal denervation exhibited neither natriuresis nor an increase in GFR in response to BilCAT despite similar vasodepression caused by the maneuver. Normotensive Wistar-Kyoto (WKY) rats responded to BilCAT like Sprague-Dawley rats, whereas spontaneously hypertensive rats (SHR) exhibited an exaggerated vasodepressor response to BilCAT (-51 +/- 3 mmHg) without increasing either UNaV or GFR. Separate groups of WKY and SHR were treated from 4 wk of age with captopril added to the drinking water at a concentration of 1 g/l. At 12-14 wk, both groups had lower MAP compared with untreated animals. Captopril treatment did not alter either the natriuretic response or the increase in GFR seen in untreated WKY after BilCAT, and the maneuver produced equivalent degrees of vasodepression as in controls. However, treated SHR now responded to BilCAT with increases in both UNaV and GFR that closely resembled the responses seen in Sprague-Dawley and WKY rats. These results suggest that BilCAT produces natriuresis through a pathway dependent on the renal nerves. This pathway does not function in untreated SHR despite similar vasodepression. Long-term treatment with captopril restores this reflex pathway in SHR, lending support to the concept that angiotensin II is critically linked to heightened sympathetic nerve activity and abnormal sodium metabolism in this strain.

Orally administered L-arginine does not alter right ventricular hypertrophy in chronically hypoxic rats

1994 ◽  
Vol 266 (2) ◽  
pp. R559-R563 ◽  
Author(s):  
T. C. Resta ◽  
B. R. Walker
Keyword(s):  
Right Ventricular ◽  
Pulmonary Circulation ◽  
Wistar Rats ◽  
Chronic Hypoxia ◽  
Chronic Administration ◽  
Hypoxic Exposure ◽  
Sprague Dawley ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilators ◽  
Sprague Dawley Rats

Evidence suggests that nitric oxide synthesis within the pulmonary circulation may be attenuated during chronic hypoxia in Wistar rats due to reduced L-arginine availability. In contrast, chronically hypoxic Sprague-Dawley rats exhibit normal endothelium-dependent pulmonary vasodilation. The purpose of the present study was to determine whether 1) Wistar rats demonstrate greater right ventricular (RV) hypertrophy in response to chronic hypoxia than Sprague-Dawley rats and 2) chronic administration of L-arginine would diminish this response in Wistar rats. L-Arginine had no effect on the degree of hypoxia-induced RV hypertrophy or polycythemia in either strain of rat. However, Wistar rats demonstrated greater hypoxia-induced RV hypertrophy and polycythemia compared with Sprague-Dawley rats. To determine whether chronically hypoxic Wistar rats indeed exhibit impaired endothelium-dependent pulmonary vasodilation, isolated lungs from control and chronically hypoxic Wistar rats were administered the endothelium-dependent pulmonary vasodilators A23187 or vasopressin. Vasodilatory responses to either agent were unaffected by chronic hypoxic exposure. We conclude that endothelium-dependent pulmonary vasodilation is maintained in the pulmonary circulation of chronically hypoxic Wistar and Sprague-Dawley rats.

Gastric leptin: a novel role in cardiovascular regulation

2010 ◽  
Vol 298 (2) ◽  
pp. H406-H414 ◽  
Author(s):  
D. M. Sartor ◽  
A. J. M. Verberne
Keyword(s):  
Cardiovascular Effects ◽  
Receptor Activation ◽  
Cardiovascular Regulation ◽  
Sprague Dawley ◽  
Inhibitory Effects ◽  
Short Term ◽  
Sprague Dawley Rats ◽  
Gut Hormone ◽  
Cervical Vagotomy ◽  
Nerve Discharge

Gastric-derived leptin affects satiety and gastrointestinal function via vagal mechanisms and has been shown to interact with the gut hormone cholecystokinin (CCK). CCK selectively inhibits splanchnic sympathetic nerve discharge (SND) and the activity of a subset of presympathetic vasomotor neurons in the rostroventrolateral medulla (RVLM). The present study sought to examine the effects of gastric leptin on arterial pressure (AP), heart rate (HR), SND, and RVLM neuronal activity to determine whether its effects on cardiovascular regulation are dependent on CCK1 receptors and vagal afferent transmission. To mimic gastric leptin, leptin (15–30 μg/kg) was administered close to the coeliac artery in anesthetized, artificially ventilated Sprague-Dawley rats. Within 5 min, leptin selectively decreased the activity of RVLM neurons also inhibited by CCK (−27 ± 4%; P < 0.001; n = 15); these inhibitory effects were abolished following administration of the CCK1 receptor antagonist lorglumide. Leptin significantly decreased AP and HR (−10 ± 2 mmHg, P < 0.001; and −8 ± 2 beats/min, P < 0.01; n = 35) compared with saline (−1 ± 2 mmHg, 3 ± 2 beats/min; n = 30). In separate experiments, leptin inhibited splanchnic SND compared with saline (−9 ± 2% vs. 2 ± 3%, P < 0.01; n = 8). Bilateral cervical vagotomy abolished the sympathoinhibitory, hypotensive, and bradycardic effects of leptin ( P < 0.05; n = 6). Our results suggest that gastric leptin may exert acute sympathoinhibitory and cardiovascular effects via vagal transmission and CCK1 receptor activation and may play a separate role to adipose leptin in short-term cardiovascular regulation.

Ampakine pretreatment enables a single hypoxic episode to produce phrenic motor facilitation with no added benefit of additional episodes

2021 ◽  
Author(s):  
Prajwal Pradeep Thakre ◽  
Michael D. Sunshine ◽  
David D. Fuller
Keyword(s):  
Ampa Receptors ◽  
Phrenic Nerve ◽  
Statistical Significance ◽  
Sprague Dawley ◽  
Hypoxic Episode ◽  
Sprague Dawley Rats ◽  
Burst Amplitude ◽  
Acute Increase ◽  
Long Term Facilitation ◽  
Sustained Increase

Repeated short episodes of hypoxia produces a sustained increase in phrenic nerve output lasting well beyond AIH exposure (i.e., phrenic long term facilitation, pLTF). Pretreatment with ampakines, drugs which allosterically modulate AMPA receptors, enables a single brief episode of hypoxia to produce pLTF, lasting up to 90 min after hypoxia. Here we tested the hypothesis that ampakine pretreatment would enhance the magnitude of pLTF evoked by repeated bouts of hypoxia. Phrenic nerve output was recorded in urethane-anesthetized, mechanically ventilated and vagotomized adult male Sprague-Dawley rats. Initial experiments demonstrated that ampakine CX717 (15 mg/kg, intravenous) caused an acute increase in phrenic nerve inspiratory burst amplitude reaching 70±48% baseline (BL) after 2 min (P=0.01. This increased bursting was not sustained (2±32%BL at 60 min, P=0.9). When CX717 was delivered 2 min prior to a single episode of isocapnic hypoxia (5-min, PaO2 = 44±9 mmHg) facilitation of phrenic nerve burst amplitude occurred (96±62%BL at 60 min, P<0.001). However, when CX717 was given 2 min prior to three, 5-min hypoxic episodes (PaO2 = 45±6 mmHg) pLTF was attenuated and did not reach statistical significance (24±29%BL, P=0.08). In the absence of CX717 pretreatment, pLTF was observed after three (74±33%BL at 60 min, P<0.001) but not one episode of hypoxia (1±8%BL at 60 min, P=0.9). We conclude that pLTF is not enhanced when ampakine pretreatment is followed by repeated bouts of hypoxia. Rather, the combination of ampakine and a single hypoxic episode appears to be ideal for producing sustained increase in phrenic motor output.

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