The role of pulmonary vascular responses to chronic hypoxia in the development of chronic mountain sickness in rats

1984 ◽  
Vol 58 (2) ◽  
pp. 171-185 ◽  
Author(s):  
Nicholas S. Hill ◽  
Lo Chang Ou
Keyword(s):  
Chronic Hypoxia ◽  
Chronic Mountain Sickness ◽  
Vascular Responses ◽  
Mountain Sickness

Role of the spleen in the exaggerated polycythemic response to hypoxia in chronic mountain sickness in rats

1999 ◽  
Vol 87 (5) ◽  
pp. 1901-1908 ◽  
Author(s):  
H. Y. Kam ◽  
L. C. Ou ◽  
C. D. Thron ◽  
R. P. Smith ◽  
J. C. Leiter
Keyword(s):  
Bone Marrow ◽  
Chronic Hypoxia ◽  
Hypoxic Exposure ◽  
Large Measure ◽  
Chronic Mountain Sickness ◽  
Fe Uptake ◽  
Rat Strain ◽  
Mountain Sickness ◽  
Rapid Appearance

In a rat model of chronic mountain sickness, the excessive polycythemic response to hypoxic exposure is associated with profound splenic erythropoiesis. We studied the uptake and distribution of radioactive iron and red blood cell (RBC) morphology in intact and splenectomized rats over a 30-day hypoxic exposure. Retention of59Fe in the plasma was correlated with59Fe uptake by both spleen and marrow and the appearance of59Fe-labeled RBCs in the blood.59Fe uptake in both the spleen and the marrow paralleled the production of nucleated RBCs. Splenic59Fe uptake was ∼10% of the total marrow uptake under normoxic conditions but increased to 60% of the total marrow uptake during hypoxic exposure. Peak splenic59Fe uptake and splenomegaly occurred at the most intense phase of erythropoiesis and coincided with the rapid appearance of59Fe-labeled RBCs in the blood. The bone marrow remains the most important erythropoietic organ under both resting and stimulated states, but inordinate splenic erythropoiesis in this rat strain accounts in large measure for the excessive polycythemia during the development of chronic mountain sickness in chronic hypoxia.

Role of sex hormones in development of chronic mountain sickness in rats

1994 ◽  
Vol 77 (1) ◽  
pp. 427-433 ◽  
Author(s):  
L. C. Ou ◽  
G. L. Sardella ◽  
J. C. Leiter ◽  
T. Brinck-Johnsen ◽  
R. P. Smith
Keyword(s):  
Gender Differences ◽  
Pulmonary Hypertension ◽  
High Altitude ◽  
Sex Hormones ◽  
Systolic Pressure ◽  
Female Rats ◽  
Hypoxic Exposure ◽  
Chronic Mountain Sickness ◽  
Mountain Sickness

After chronic exposure to hypoxia, Hilltop Sprague-Dawley rats developed excessive polycythemia and severe pulmonary hypertension and right ventricular (RV) hypertrophy, signs consistent with human chronic mountain sickness; however, there were gender differences in the magnitude of the polycythemia and susceptibility to the fatal consequence of chronic mountain sickness. Orchiectomy and ovariectomy were performed to evaluate the role of sex hormones in the gender differences in these hypoxic responses. After 40 days of exposure to simulated high altitude (5,500 m; barometric pressure of 370 Torr and inspired Po2 of 73 Torr), both sham-gonadectomized male and female rats developed polycythemia and had increased RV peak systolic pressure and RV hypertrophy. The hematocrit was slightly but significantly higher in males than in females. Orchiectomy did not affect these hypoxic responses, although total ventricular weight was less in the castrated high-altitude rats. At high altitude, the mortality rates were 67% in the sham-operated male rats and 50% in the castrated animals. In contrast, ovariectomy aggravated the high-altitude-associated polycythemia and increased RV peak systolic pressure and RV weight compared with the sham-operated high-altitude female rats. Both sham-operated control and ovariectomized females suffered negligible mortality at high altitude. The present study demonstrated that 1) the male sex hormones play no role in the development of the excessive polycythemia, pulmonary hypertension, and RV hypertrophy during chronic hypoxic exposure or in the associated high mortality and 2) the female sex hormones suppressed both the polycythemic and cardiopulmonary responses in vivo during chronic hypoxic exposure.

The role of menopause in the development of chronic mountain sickness

1997 ◽  
Vol 272 (1) ◽  
pp. R90-R94 ◽  
Author(s):  
F. Leon-Velarde ◽  
M. A. Ramos ◽  
J. A. Hernandez ◽  
D. De Idiaquez ◽  
L. S. Munoz ◽  
...  
Keyword(s):  
Premenopausal Women ◽  
Signs And Symptoms ◽  
Blood Oxygen ◽  
Blood Oxygen Saturation ◽  
Chronic Mountain Sickness ◽  
Female Population ◽  
Mountain Sickness ◽  
Cerro De Pasco ◽  
Expiratory Flow Rates

The objective of this study was to investigate the role of menopause in the appearance of the physiopathological sequence that leads to chronic mountain sickness (CMS) in a high-altitude female population. The females studied are 30-54 yr old (n = 152) and have permanent residence in Cerro de Pasco (Pasco, Peru; 4,300 m). The sample was divided into postmenopausal and premenopausal groups for comparison. Blood oxygen saturation (SaO2), excessive erythrocytosis [EE, measured by the level of hematocrit (Het)], peak expiratory flow rates (PEFR), and a score that represents the main signs and symptoms of CMS (CMSscore) were measured. Postmenopausal women had higher Het (50.2 +/- 4.04 vs. 47.4 +/- 4.13%, P < 0.001), lower SaO2 (81.9 +/- 4.12 vs. 84.7 +/- 3.14%, P < 0.001) and PEFR values (489 +/- 101 vs. 534 +/- 90 l/min, P < 0.02), and slightly higher CMSscore (19.1 +/- 3.37 vs. 17.9 +/- 3.48, P < 0.06) than premenopausal women. The prevalence of women with EE (EE = Hct > 56%) was found to be 8.8%. Forty-five percent of the postmenopausal subjects presented a high CMSscore (> 21), whereas only 22% of the premenopausal subjects presented this high value (P < 0.02). We can therefore conclude that menopause may represent a contributing factor for the development of CMS.

scholarly journals Optimal hemoglobin concentration and high altitude: a theoretical approach for Andean men at rest

2004 ◽  
Vol 96 (5) ◽  
pp. 1581-1588 ◽  
Author(s):  
Francisco C. Villafuerte ◽  
Rosa Cárdenas ◽  
Carlos Monge-C
Keyword(s):  
Cardiac Output ◽  
Theoretical Analysis ◽  
High Altitude ◽  
Hemoglobin Concentration ◽  
Mathematical Approach ◽  
Chronic Mountain Sickness ◽  
Physiological Variables ◽  
Mixed Mean ◽  
Mountain Sickness

The beneficial role of erythrocytosis for O2 transport has been questioned by evidence from bloodletting and hemodilution research as well as by studies suggesting the existence of an “optimal” hematocrit (Hct) or hemoglobin concentration ([Hb]) value. To assess to what extent erythrocytosis is beneficial in Andean men at high altitude, we examined and discussed optimal [Hb] using a mathematical approach by modeling the mixed (mean) venous Po2 (Pv̄O2) and arterial O2 content, considering for both the relation between [Hb] and arterial Po2. Relations of [Hb] to other physiological variables such as cardiac output and convective arterial O2 transport were also discussed, revealing the importance of Pv̄O2 in this model. Our theoretical analysis suggests that increasing [Hb] allows increase and maintenance of Pv̄O2 with only moderate declines in arterial Po2 as a consequence of moderate increases in altitude, reaching its maximum at the optimal [Hb] of 14.7 g/dl. Our analysis also shows that [Hb] corresponding to high arterial O2 content and O2 transport values is apparently not quite advantageous for improvement of oxygenation. Furthermore, chronic mountain sickness is discussed as an insightful example of the effects of excessive erythrocytosis at high altitude.

Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness

1997 ◽  
Vol 83 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Gene L. Colice ◽  
Nicholas Hill ◽  
Yan-Jie Lee ◽  
Hongkai Du ◽  
James Klinger ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Single Dose ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Minute Ventilation ◽  
Chronic Mountain Sickness ◽  
Pulmonary Vascular Remodeling ◽  
Increased Sensitivity ◽  
Pulmonary Arterial ◽  
Mountain Sickness

Colice, Gene L., Nicholas Hill, Yan-Jie Lee, Hongkai Du, James Klinger, James C. Leiter, and Lo-Chang Ou. Exaggerated pulmonary hypertension with monocrotaline in rats susceptible to chronic mountain sickness. J. Appl. Physiol. 83(1): 25–31, 1997.—Hilltop (H) strain Sprague-Dawley rats are more susceptible to chronic mountain sickness than are the Madison (M) strain rats. It is unclear what role pulmonary vascular remodeling, polycythemia, and hypoxia-induced vasoconstriction play in mediating the more severe pulmonary hypertension that develops in the H rats during chronic hypoxia. It is also unclear whether the increased sensitivity of the H rats to chronic mountain sickness is specific for a hypoxia effect or, instead, reflects a general propensity toward the development of pulmonary hypertension. Monocrotaline (MCT) causes pulmonary vascular remodeling and pulmonary hypertension. We hypothesized that the difference in the pulmonary vascular response to chronic hypoxia between H and M rats reflects an increased sensitivity of the H rats to any pulmonary hypertensive stimuli. Consequently, we expected the two strains to also differ in their susceptibility to MCT-induced pulmonary hypertension. Pulmonary arterial pressures in conscious H and M rats were measured 3 wk after a single dose of MCT, exposure to a simulated high altitude of 18,000 ft (barometric pressure = 380 mmHg), and administration of a single dose of saline as a placebo. The H rats had significantly higher pulmonary arterial pressures and right ventricular weights after MCT and chronic hypoxia than did the M rats. The H rats also had more pulmonary vascular remodeling, i.e., greater wall thickness as a percentage of vessel diameter, after MCT and chronic hypoxia than did the M rats. The H rats had significantly lower arterial[Formula: see text] than did the M rats after MCT, but the degree of hypoxemia was mild [arterial[Formula: see text] of 72.5 ± 0.8 (SE) Torr for H rats vs. 77.4 ± 0.8 Torr for M rats after MCT]. The H rats had lower arterial [Formula: see text] and larger minute ventilation values than did the M rats after MCT. These ventilatory differences suggest that MCT caused more severe pulmonary vascular damage in the H rats than in the M rats. These data support the hypothesis that the H rats have a general propensity to develop pulmonary hypertension and suggest that differences in pulmonary vascular remodeling account for the increased susceptibility of H rats, compared with M rats, to both MCT and chronic hypoxia-induced pulmonary hypertension.

scholarly journals Association of Age with the Expression of Hypoxia-Inducible Factors HIF-1α, HIF-2α, HIF-3α and VEGF in Lung and Heart of Tibetan Sheep

Animals ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 673 ◽  
Author(s):  
Yanyu He ◽  
John S Munday ◽  
Matthew Perrott ◽  
Guan Wang ◽  
Xiu Liu
Keyword(s):  
Gene Expression ◽  
Alveolar Macrophages ◽  
Physiological Response ◽  
Hypoxia Inducible Factors ◽  
Low Oxygen ◽  
Cardiac Muscle Cells ◽  
Chronic Mountain Sickness ◽  
Tibetan Sheep ◽  
Mountain Sickness

Hypoxia-inducible factors (HIFs) play an important role in mediating the physiological response to low oxygen environments. However, whether the expression of HIFs changes with age is unknown. In the present study, the effect of aging on HIF-1α, HIF-2α, HIF-3α and VEGF expression in the heart and lung of 30 Tibetan sheep that were adapted to hypoxia was evaluated. The 30 sheep were subdivided into groups of 10 animals that were 1, 2 or 6 years of age. Immunohistochemistry for HIF-1α, HIF-2α, HIF-3α and VEGF revealed that the immunostaining intensity of VEGF protein in the heart and lung was significantly higher than the intensity of immunostaining against the HIFs (p < 0.05). HIF-1α and HIF-2α protein translocated into the nucleus of cardiac muscle cells. However, immunostaining for HIF-3α was restricted to the cytoplasm of the myocardial cells. Immunostaining for HIF-1α, HIF-2α, HIF-3α and VEGF was detected within alveolar macrophages. The concentration of HIF-1α and HIF-2α was higher in the lung of 1-year-old than 6-year-old sheep (p < 0.05). In contrast, HIF-3α and VEGF immunostaining was most prominent in the hearts of the oldest sheep. However, when RT-PCR was used to evaluate RNA within the tissues, the expression of all four studied genes was higher in the lung than in the heart in the 1-year-old sheep (p < 0.05). Furthermore, VEGF and HIF-3α gene expression was higher in the heart from 1-year old than 6-year old sheep (p < 0.05). However, in the lung, HIF-1α and HIF-2α gene expression was lower in 1-year old than 6-year old sheep (p < 0.05). We conclude that HIF-3α and VEGF may play be important in how the heart responds to hypoxia. Additionally, HIF-1α and HIF-2α may have a role in the adaptation of the lung to hypoxia. The expression of these proteins in alveolar macrophages suggests a potential role of these cells in the physiological response to hypoxia. These results are useful in understanding how age influences the hypoxia adaption mechanisms of the heart and lung and may help to better understand chronic mountain sickness that is commonly observed in Tibetan people living on the Qinghai-Tibetan plateau.

scholarly journals New genetic and physiological factors for excessive erythrocytosis and Chronic Mountain Sickness

2015 ◽  
Vol 119 (12) ◽  
pp. 1481-1486 ◽  
Author(s):  
Francisco C. Villafuerte
Keyword(s):  
High Altitude ◽  
Hypoxia Inducible Factor ◽  
Physiological Factors ◽  
Chronic Mountain Sickness ◽  
Functional Studies ◽  
Differential Expression Pattern ◽  
Its Gene ◽  
Specific Protease ◽  
Mountain Sickness

In the last few years, genetic and functional studies have provided important insight on the pathophysiology of excessive erythrocytosis (EE), the main sign of Chronic Mountain Sickness (CMS). The recent finding of the association of the CMS phenotype with a single-nucleotide polymorphism (SNP) in the Sentrin-specific Protease 1 ( SENP1) gene, and its differential expression pattern in Andean highlanders with and without CMS, has triggered large interest in high-altitude studies because of the potential role of its gene product in the control of erythropoiesis. The SENP1 gene encodes for a protease that regulates the function of hypoxia-relevant transcription factors such as Hypoxia-Inducible Factor (HIF) and GATA, and thus might have an erythropoietic regulatory role in CMS through the modulation of the expression of erythropoietin (Epo) or Epo receptors. The different physiological patterns in the Epo-EpoR system found among Andeans, even among highlanders with CMS, together with their different degrees of erythropoietic response, might indicate specific underlying genetic backgrounds, which in turn might reflect different levels of adaptation to lifelong high-altitude hypoxia. This minireview discusses recent genetic findings potentially underlying EE and CMS, and their possible physiological mechanisms in Andean highlanders.

Breathing and its stimulatory responses in parkinsonism: repercussions for physiotherapy

2020 ◽  
Author(s):  
Mieczyslaw Pokorski
Keyword(s):  
Experimental Study ◽  
Chronic Hypoxia ◽  
Motor Impairments

This study addresses respiratory and motor impairments in an experimental reserpine-induced model of parkinsonism in rats. The role of chronic hypoxia due to diminished ventilation in the development and course of neurodegeneration is addressed. An attempt was made to distinguish between central and peripheral dopamine pathways in the mechanisms of neurodegeneration. A dissociation of putative mechanisms of respiratory and motor impairments is tackled as well. Although this purely experimental study cannot be directly extrapolated to human pathophysiology, the corollaries have been drawn concerning the potential repercussions of the respiratory and motor impairments for the physiotherapeutic procedures in the management of chronic neurodegeneration.

Sign in / Sign up

Export Citation Format

Share Document