scholarly journals Mice and Rats Display Different Ventilatory, Hematological, and Metabolic Features of Acclimatization to Hypoxia

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Arias-Reyes ◽  
Jorge Soliz ◽  
Vincent Joseph
Keyword(s):  
High Altitude ◽  
Minute Ventilation ◽  
Rattus Rattus ◽  
Hemoglobin Concentration ◽  
Whole Body ◽  
Ecological Niches ◽  
House Mice ◽  
Sprague Dawley ◽  
Mitochondrial Oxygen Consumption ◽  
Sd Rats

Phylogeographic studies showed that house mice (Mus musculus) originated in the Himalayan region, while common rats (Rattus rattus and Rattus norvegicus) come from the lowlands of China and India. Accordingly, it has been proposed that its origins gave mice, but not rats, the ability to invade ecological niches at high altitudes (pre-adaptation). This proposal is strongly supported by the fact that house mice are distributed throughout the world, while common rats are practically absent above 2,500 m. Considering that the ability of mammals to colonize high-altitude environments (>2,500 m) is limited by their capability to tolerate reduced oxygen availability, in this work, we hypothesize that divergences in the ventilatory, hematological, and metabolic phenotypes of mice and rats establish during the process of acclimatization to hypoxia (Hx). To test this hypothesis male FVB mice and Sprague-Dawley (SD) rats were exposed to Hx (12% O2) for 0 h (normoxic controls), 6 h, 1, 7, and 21 days. We assessed changes in ventilatory [minute ventilation (VE), respiratory frequency (fR), and tidal volume (VT)], hematological (hematocrit and hemoglobin concentration), and metabolic [whole-body O2 consumption (VO2) and CO2 production (VCO2), and liver mitochondrial oxygen consumption rate (OCR) parameters]. Compared to rats, results in mice show increased ventilatory, metabolic, and mitochondrial response. In contrast, rats showed quicker and higher hematological response than mice and only minor ventilatory and metabolic adjustments. Our findings may explain, at least in part, why mice, but not rats, were able to colonize high-altitude habitats.

scholarly journals The Role of Carotid Sinus Nerve Input in the Hypoxic-Hypercapnic Ventilatory Response in Juvenile Rats

2020 ◽  
Vol 11 ◽  
Author(s):  
Paulina M. Getsy ◽  
Gregory A. Coffee ◽  
Stephen J. Lewis
Keyword(s):  
Carotid Sinus ◽  
Nucleus Tractus Solitarius ◽  
Minute Ventilation ◽  
Respiratory Pattern ◽  
Whole Body ◽  
Carotid Sinus Nerve ◽  
Sprague Dawley ◽  
Juvenile Rats ◽  
Ventilatory Responses ◽  
Chemosensory Pathway

In juvenile rats, the carotid body (CB) is the primary sensor of oxygen (O2) and a secondary sensor of carbon dioxide (CO2) in the blood. The CB communicates to the respiratory pattern generator via the carotid sinus nerve, which terminates within the commissural nucleus tractus solitarius (cNTS). While this is not the only peripheral chemosensory pathway in juvenile rodents, we hypothesize that it has a unique role in determining the interaction between O2 and CO2, and consequently, the response to hypoxic-hypercapnic gas challenges. The objectives of this study were to determine (1) the ventilatory responses to a poikilocapnic hypoxic (HX) gas challenge, a hypercapnic (HC) gas challenge or a hypoxic-hypercapnic (HH) gas challenge in juvenile rats; and (2) the roles of CSN chemoafferents in the interactions between HX and HC signaling in these rats. Studies were performed on conscious, freely moving juvenile (P25) male Sprague Dawley rats that underwent sham-surgery (SHAM) or bilateral transection of the carotid sinus nerves (CSNX) 4 days previously. Rats were placed in whole-body plethysmographs to record ventilatory parameters (frequency of breathing, tidal volume and minute ventilation). After acclimatization, they were exposed to HX (10% O2, 90% N2), HC (5% CO2, 21% O2, 74% N2) or HH (5% CO2, 10% O2, 85% N2) gas challenges for 5 min, followed by 15 min of room-air. The major findings were: (1) the HX, HC and HH challenges elicited robust ventilatory responses in SHAM rats; (2) ventilatory responses elicited by HX alone and HC alone were generally additive in SHAM rats; (3) the ventilatory responses to HX, HC and HH were markedly attenuated in CSNX rats compared to SHAM rats; and (4) ventilatory responses elicited by HX alone and HC alone were not additive in CSNX rats. Although the rats responded to HX after CSNX, CB chemoafferent input was necessary for the response to HH challenge. Thus, secondary peripheral chemoreceptors do not compensate for the loss of chemoreceptor input from the CB in juvenile rats.

Changes in respiratory timing induced by hypercapnia in maturing rats

1999 ◽  
Vol 87 (2) ◽  
pp. 484-490 ◽  
Author(s):  
Jalal M. Abu-Shaweesh ◽  
Ismail A. Dreshaj ◽  
Agnes J. Thomas ◽  
Musa A. Haxhiu ◽  
Kingman P. Strohl ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Aminobutyric Acid ◽  
Whole Body ◽  
Sprague Dawley ◽  
Newborn Rat ◽  
Rat Pups ◽  
Significant Prolongation ◽  
Sprague Dawley Rats ◽  
Central Origin

Premature infants respond to hypercapnia by an attenuated ventilatory response that is characterized by a decrease in respiratory frequency. We hypothesized that this impaired hypercapnic ventilatory response is of central origin and is mediated via γ-aminobutyric acid-ergic (GABAergic) pathways. We therefore studied two groups of maturing Sprague-Dawley rats: unrestrained rats in a whole body plethysmograph at four postnatal ages (5, 16–17, 22–23, and 41–42 days); and ventilated, decerebrate, vagotomized, paralyzed rats in which phrenic nerve responses to hypercapnia were measured at 4–6 and 37–39 days of age. In the unrestrained group, the increase in minute ventilation induced by hypercapnia was significantly lower at 5 days vs. beyond 16 days. Although there was an increase in tidal volume at all ages, frequency decreased significantly from baseline at 5 days, whereas it increased significantly at 16–17, 22–23, and 41–42 days. The decrease in frequency at 5 days of age was mainly due to a significant prolongation in expiratory duration (Te). In the ventilated group, hypercapnia also caused prolongation in Te at 4–6 days but not at 37–39 days of age. Intravenous administration of bicuculline (GABAA-receptor blocker) abolished the prolongation of Te in response to hypercapnia in the newborn rats. We conclude that newborn rat pups exhibit a characteristic ventilatory response to CO2 expressed as a centrally mediated prolongation of Te that appears to be mediated by GABAergic mechanisms.

Susceptibility to high-altitude pulmonary edema in Madison and Hilltop rats. I. Ventilation and fluid balance

1995 ◽  
Vol 78 (6) ◽  
pp. 2279-2285
Author(s):  
G. L. Colice ◽  
Y. J. Lee ◽  
J. Chen ◽  
H. K. Du ◽  
G. Ramirez ◽  
...  
Keyword(s):  
Pulmonary Edema ◽  
High Altitude ◽  
Minute Ventilation ◽  
Plasma Renin ◽  
Barometric Pressure ◽  
Simulated Altitude ◽  
Sprague Dawley ◽  
Lung Water ◽  
Fluid Handling ◽  
High Altitude Pulmonary Edema

The pathogenesis of high-altitude pulmonary edema (HAPE) is not well understood. Ventilation and fluid-handling abnormalities at high altitude (HA) may play a role in HAPE. Because ventilatory and cardiopulmonary responses to chronic HA exposure in the Hilltop (H) strain of Sprague-Dawley rat are different from those in the Madison (M) strain, it was hypothesized that these strains would have different susceptibilities to developing HAPE. M and H rats were studied at sea level (SL) and in a hypobaric chamber after 9 and 12 h at a simulated altitude of 24,000 ft (barometric pressure = 295 mmHg) and 1, 12, and 24 h at a simulated altitude of 18,000 ft (barometric pressure = 380 mmHg). Both strains developed HAPE, but the M rat was more susceptible to HAPE, as demonstrated by a higher mortality rate from hemorrhagic pulmonary edema after 9 h at 24,000 ft and an earlier increase in lung water after exposure to 18,000 ft. Minute ventilation was similar in both strains at HA, but arterial PO2 was significantly higher in the M rat. Both strains had a significant decrease in fluid intake and negative sensible water balance at HA. No changes in plasma renin activity, aldosterone concentrations, antidiuretic hormone levels, and atrial natriuretic peptide levels were found at HA. The increased susceptibility of the M rat to HAPE is therefore not explained by ventilation or fluid-handling abnormalities.

Abstract 400: Angiotensin II Triggers the Same Pressor Mechanisms in Salt-sensitive Hypertension and During Salt Depletion

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Mordecai P Blaustein ◽  
Ling Chen ◽  
Meng Li ◽  
Junjie Gao ◽  
John M Hamlyn
Keyword(s):  
Mesenteric Arteries ◽  
Whole Body ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Dietary Salt ◽  
Sd Rats ◽  
Multi Stage ◽  
Salt Depletion ◽  
Transporter Expression

Salt restriction or blood volume decline activates the renin-angiotensin (Ang) system to protect against short- and long-term drops in blood pressure (BP). Excess dietary salt and salt retention, however, activates CNS Ang II-mediated mechanisms that elevate BP. We tested the idea that the same CNS-regulated downstream mechanisms modulate total peripheral vascular resistance (TPR) under both conditions. Protocol 1: normal Sprague-Dawley (SD) rats were fed either normal salt (NS, 0.4% NaCl) or low salt (LS, 0.1% NaCl) for 2 wks. Protocol 2: SD rats were infused subcutaneously with vehicle (V, saline) or Ang II (A, 150 ng/kg/min); some V and some A rats were fed NS, and the others were fed high salt (HS, 2% NaCl) for 2 wks. At the end of both protocols, intra-arterial BP was recorded and blood was drawn for endogenous ouabain (EO) determination by radioimmunoassay and multi-stage mass spectroscopy. Aortae and mesenteric arteries were harvested for protein immunoblots to determine arterial smooth muscle (ASM) expression of Na/Ca exchanger-1 (NCX1), a key Ca 2+ transporter. LS did not affect mean BP (87±2 vs 91±4 mm Hg, n =6 each), but did raise plasma EO (0.70±0.19 vs 0.21±0.02 nM, P < 0.05) and increase ASM NCX1 expression 1.52-fold. Ang II infusion and, especially, HS + Ang II, increased mean BP (110±4 and 124±3 mm Hg, P <0.05 and P <0.001, respectively, vs 100±4 mm Hg, n =5-8) and plasma EO (0.53±0.31 and 1.31±0.72 nM, respectively, both P<0.05, vs 0.07±0.02 nM, n =5-8). HS + Ang II also increased ASM NCX1 expression 1.91-fold. HS + Ang II, as well as LS also increased expression of SERCA2 and TRPC6, two other ASM Ca 2+ transporters. Intracerebroventricular Ang II also raises plasma EO and increases expression of the 3 Ca 2+ transporters in ASM; thus, the CNS controls this pressor pathway (Hamlyn et al., Hypertension 60 (3, Suppl.):e419, 2012). The new data reveal that both LS and HS activate the same downstream mechanisms: they elevate plasma EO and ASM Ca 2+ transporter expression. The increases in ASM Ca 2+ transporter expression, and enhanced sympathetic drive, should increase arterial tone and raise BP during salt excess, and minimize BP decline. We conclude that these fundamental mechanisms contribute to “whole body autoregulation” in the long-term control of TPR and BP.

Changes in Myoglobin Content of the High Altitude Acclimatized Rat

1956 ◽  
Vol 185 (3) ◽  
pp. 549-556 ◽  
Author(s):  
Burton E. Vaughan ◽  
Nello Pace
Keyword(s):  
High Altitude ◽  
Sea Level ◽  
Hemoglobin Concentration ◽  
The Body ◽  
Whole Body ◽  
Altitude Exposure ◽  
Cell Plasma ◽  
Muscle Groups ◽  
Cellular Oxidation ◽  
Total Body

A method is described for the assay of myoglobin in all myoglobin containing tissues of the rat, in particular the heart and diaphragm. Total body myoglobin increased 70% above sea level values, both in animals taken from sea level to 12,500 feet and in animals born and reared at 12,500 feet. In comparison with the muscle hemoglobin concentration increase of 50%, the blood hemoglobin concentration increased only 25% above sea level values. Whole body content of myoglobin was determined directly, and this amounted to 17.3 mg/100 gm of body weight, or to 42.3 mg/100 gm of wet muscle. Partition of the body myoglobin among seven muscle groups was ascertained. Heart, diaphragm and the two masseters contain only about 10% of the total myoglobin. Evaluation was made of the factors that have been suggested to explain the disparity in the originally reported myoglobin increases at high altitude of Hurtado et al. and more recent work. It is clear that failure to obtain the increase in the rat is attributable to the use of intermittent rather than continuous high altitude exposure. Evidence for full acclimatization in the animals here used was adduced. The suggestion is made that myoglobin maintains an optimal oxygen gradient between the cell plasma membrane and the mitochondria, and in so doing is involved in dynamic relation to cellular oxidation.

Propranolol does not impair exercise oxygen uptake in normal men at high altitude

1986 ◽  
Vol 61 (5) ◽  
pp. 1935-1941 ◽  
Author(s):  
L. G. Moore ◽  
A. Cymerman ◽  
S. Y. Huang ◽  
R. E. McCullough ◽  
R. G. McCullough ◽  
...  
Keyword(s):  
High Altitude ◽  
Minute Ventilation ◽  
Hemoglobin Concentration ◽  
Adrenergic Blockade ◽  
Adrenergic Stimulation ◽  
O2 Uptake ◽  
Compensatory Mechanisms ◽  
Beta Adrenergic ◽  
Propranolol Treatment ◽  
Normal Men

Decreased maximal O2 uptake (VO2max) and stimulation of the sympathetic nervous system have been previously shown to occur at high altitude. We hypothesized that tachycardia mediated by beta-adrenergic stimulation acted to defend VO2max at high altitude. Propranolol treatment beginning before high-altitude (4,300 m) ascent reduced heart rate during maximal and submaximal exercise in six healthy men treated with propranolol (80 mg three times daily) compared with five healthy subjects receiving placebo (lactose). Compared with sea-level values, the VO2max fell on day 2 at high altitude, but the magnitude of fall was similar in the placebo and propranolol treatment groups (26 +/- 6 vs. 32 +/- 5%, P = NS) and VO2max remained similar at high altitude in both groups once treatment was discontinued. During 30 min of submaximal (80% of VO2max) exercise, propranolol-treated subjects maintained O2 uptake levels that were as large as those in placebo subjects. The maintenance of maximal or submaximal levels of O2 uptake in propranolol-treated subjects at 4,300 m could not be attributed to increased minute ventilation, arterial O2 saturation, or hemoglobin concentration. Rather, it appeared that propranolol-treated subjects maintained O2 uptake by transporting a greater proportion of the O2 uptake with each heartbeat. Thus, contrary to our hypothesis, beta-adrenergic blockade did not impair maximal or submaximal O2 uptake at high altitude due perhaps to compensatory mechanisms acting to maintain stroke volume and cardiac output.

Physiological dead space increases during initial hours of chronic hypoxemia with or without hypocapnia

1994 ◽  
Vol 77 (3) ◽  
pp. 1526-1531 ◽  
Author(s):  
E. B. Olson
Keyword(s):  
Dead Space ◽  
Minute Ventilation ◽  
Volume Ratio ◽  
Whole Body ◽  
Co2 Production ◽  
Sprague Dawley ◽  
Arterial Pco2 ◽  
Physiological Dead Space ◽  
Production Ratio ◽  
Arterial Blood

A whole body plethysmograph was used to determine the minute ventilation-to-CO2 production ratio (VE/VCO2) of intact unrestrained unanesthetized adult male Sprague-Dawley rats during 7 days of hypoxemia (arterial PO2 approximately 50 Torr). In one set of rats, normocapnia (arterial PCO2 approximately 40 Torr) was maintained. Arterial blood gases and acid-base status were determined, and arterial PCO2 was used to calculate alveolar ventilation-to-VCO2 ratio (VA/VCO2) in all situations when inhaled CO2 was not elevated. In normoxia VE/VCO2 = 25 +/- 1 (mean +/- 95% confidence limits); after 12 h of hypoxemia, VE/VCO2 was maximal, 61 +/- 5 in hypoxemic hypocapnia and 200 +/- 55 in hypoxemic normocapnia. Between 2 and 7 days of hypoxemia, VE/VCO2 had plateaued, 42 +/- 3 in hypoxemic hypocapnia and 95 +/- 19 in hypoxemic normocapnia. Dead space-to-tidal volume ratio (VD/VT) = (VE/VCO2 - VA/VCO2)/(VE/VCO2), and in normoxia VD/VT = 0.17 +/- 0.04. In hypoxemic hypocapnia, VD/VT measured between 1 and 5 h was 0.38 +/- 0.04. It remained elevated at 0.29 +/- 0.04 after 24 h, but after 4-7 days in hypoxemic hypocapnia, VD/VT had recovered to 0.15 +/- 0.03. It is postulated that the disproportionate increase in VE/VCO2 observed during the first 24 h of exposure to hypoxemic normocapnia (compared with elevated steady-state plateau levels maintained from 2 to 7 days sojourn) reflects an immediate transient increase of physiological dead space on exposure to hypoxemia.

scholarly journals Episodic stimulation of central chemoreceptor neurons elicits disordered breathing and autonomic dysfunction in volume overload heart failure

2020 ◽  
Vol 318 (1) ◽  
pp. L27-L40 ◽  
Author(s):  
Hugo S. Díaz ◽  
David C. Andrade ◽  
Camilo Toledo ◽  
Katherin V. Pereyra ◽  
Karla G. Schwarz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Autonomic Dysfunction ◽  
Minute Ventilation ◽  
Volume Overload ◽  
Whole Body ◽  
Apnea Hypopnea Index ◽  
Sprague Dawley ◽  
Retrotrapezoid Nucleus ◽  
Cardiorespiratory Function ◽  
Sprague Dawley Rats

Enhanced central chemoreflex (CC) gain is observed in volume overload heart failure (HF) and is correlated with autonomic dysfunction and breathing disorders. The aim of this study was to determine the role of the CC in the development of respiratory and autonomic dysfunction in HF. Volume overload was surgically created to induce HF in male Sprague-Dawley rats. Radiotelemetry transmitters were implanted for continuous monitoring of blood pressure and heart rate. After recovering from surgery, conscious unrestrained rats were exposed to episodic hypercapnic stimulation [EHS; 10 cycles/5 min, inspiratory fraction of carbon dioxide ([Formula: see text]) 7%] in a whole body plethysmograph for recording of cardiorespiratory function. To determine the contribution of CC to cardiorespiratory variables, selective ablation of chemoreceptor neurons within the retrotrapezoid nucleus (RTN) was performed via injection of saporin toxin conjugated to substance P (SSP-SAP). Vehicle-treated rats (HF+Veh and Sham+Veh) were used as controls for SSP-SAP experiments. Sixty minutes post-EHS, minute ventilation was depressed in sham animals relative to HF animals (ΔV̇e: −5.55 ± 2.10 vs. 1.24 ± 1.35 mL/min 100 g, P < 0.05; Sham+Veh vs. HF+Veh). Furthermore, EHS resulted in autonomic imbalance, cardiorespiratory entrainment, and ventilatory disturbances in HF+Veh but not Sham+Veh rats, and these effects were significantly attenuated by SSP-SAP treatment. Also, the apnea-hypopnea index (AHI) was significantly lower in HF+SSP-SAP rats compared with HF+Veh rats (AHI: 5.5 ± 0.8 vs. 14.4 ± 1.3 events/h, HF+SSP-SAP vs. HF+Veh, respectively, P < 0.05). Finally, EHS-induced respiratory-cardiovascular coupling in HF rats depends on RTN chemoreceptor neurons because it was reduced by SSP-SAP treatment. Overall, EHS triggers ventilatory plasticity and elicits cardiorespiratory abnormalities in HF that are largely dependent on RTN chemoreceptor neurons.

Life-long consequences of postnatal normoxia exposure in rats raised at high altitude

2012 ◽  
Vol 112 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Delphine Lumbroso ◽  
Alexandra Lemoine ◽  
Marcelino Gonzales ◽  
Gabriela Villalpando ◽  
Tommy Seaborn ◽  
...  
Keyword(s):  
Right Ventricular ◽  
High Altitude ◽  
Ventricular Hypertrophy ◽  
Minute Ventilation ◽  
Right Ventricular Hypertrophy ◽  
Male Rats ◽  
Whole Body ◽  
La Paz ◽  
Respiratory Parameters ◽  
Air Space

We tested the hypothesis that exposure of high-altitude (HA) rats to a period of postnatal normoxia has long-term consequences on the ventilatory and hematological acclimatization in adults. Male and female HA rats (3,600 m, Po2 ≃ 100 Torr; La Paz, Bolivia) were exposed to normal room air [HA control (HACont)] or enriched oxygen (32% O2; Po2 ≃ 160 Torr) from 1 day before to 15 days after birth [HA postnatal normoxia (HApNorm)]. Hematocrit and hemoglobin values were assessed at 2, 12, and 32 wk of age. Cardiac and lung morphology were assessed at 12 wk by measuring right ventricular hypertrophy (pulmonary hypertension index) and lung air space-to-tissue ratio (indicative of alveolarization). Respiratory parameters under baseline conditions and in response to 32% O2 for 10 min (relieving the ambient hypoxic stimulus) were measured by whole body plethysmography at 12 wk. Finally, we performed a survival analysis up to 600 days of age. Compared with HACont, HApNorm rats had reduced hematocrit and hemoglobin levels at all ages (both sexes); reduced right ventricular hypertrophy (both sexes); lower air space-to-tissue ratio in the lungs (males only); reduced CO2 production rate, but higher oxygen uptake (males only); and similar respiratory frequency, tidal volume, and minute ventilation. When breathing 32% O2, HApNorm male rats had a stronger decrease of minute ventilation than HACont. HApNorm rats had a marked tendency toward longer survival throughout the study. We conclude that exposure to ambient hypoxia during postnatal development in HA rats has deleterious consequences on acclimatization to hypoxia as adults.

Cardioprotection is strain dependent in rat in response to whole body hyperthermia

2001 ◽  
Vol 280 (3) ◽  
pp. H1208-H1214 ◽  
Author(s):  
Hemal H. Patel ◽  
Anna Hsu ◽  
Garrett J. Gross
Keyword(s):  
Heat Shock ◽  
Infarct Size ◽  
Whole Body ◽  
Sprague Dawley ◽  
Whole Body Hyperthermia ◽  
Sd Rats ◽  
Control Versus ◽  
And Control ◽  
Temperature Time ◽  
Strain Dependent

Previous results showed a genetic component to cardioprotection. Therefore, we investigated the heat shock response in Wistar and Sprague-Dawley (SD) rats at 24 and 48 h. Rats were subjected to whole body hyperthermia achieving colonic temperatures of 40 or 42°C for 20 min. After recovery hearts were excised for protein measurements or were subjected to 30 min of ischemia and then 2 h of reperfusion. Heat shock protein (HSP) expression was determined by Western blotting and infarct size was determined by triphenyltetrazolium staining. All groups of SD and Wistar rats demonstrated HSP72 and HSP90 induction at both time points in response to a heat stress of 42°C. At 24 h there was only a significant reduction in infarct size seen in control vs. small SD (60.0 ± 4.8 vs. 26.5 ± 2.3) rats. However, at 48 h control versus small SD (60.0 ± 4.8 vs. 17.6 ± 3.8) and Wistar (59.4 ± 4.3 vs. 29.8 ± 6.0) and control versus large SD (53.7 ± 2.6 vs. 19.8 ± 4.7) and Wistar (57.3 ± 1.6 vs. 34.5 ± 2.8) rats demonstrated a significant reduction in infarct size with a greater reduction observed in SD rats. We conclude that heat shock-induced cardioprotection in rats is dependent on strain, temperature, time after stress, and size.

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