Physiological responses of rats to intermittent high-altitude stress: effects of age.

McGrath, James J.; Procházka, J; Pelouch, V.; Ošťádal, B

doi:10.1152/jappl.1973.34.3.289

Cited by 53 publications

(30 citation statements)

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“…Several investigations have been performed in rats, evaluating effects of intermittent hypoxia (IH) on pulmonary haemodynamics [27][28][29][30][31]. Severe hypoxia was applied in a hypobaric chamber for 4-8 h?day -1 , 5-7 days a week, with a total of 13-24 exposures.…”

Section: Intermittent Hypoxia In Animal Modelsmentioning

confidence: 99%

Effects of intermittent hypoxia on pulmonary haemodynamics: animal modelsversusstudies in humans

Zieliński¹

2005

Eur Respir J

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The aim of this review was to analyse the effects of intermittent hypoxia (IH) on pulmonary haemodynamics, comparing results of animal experiments with results of clinical studies.In animal investigations even short hypoxic exposure, continuously or in short repeated episodes mimicking obstructive sleep apnoea (OSA), leads to pulmonary artery remodelling and to pulmonary hypertension (PH). Results of investigations on effects of nocturnal IH on pulmonary haemodynamics in patients with chronic obstructive pulmonary disease (COPD) are discordant. Earlier studies reported the development of mild PH in subjects desaturating during sleep, while more recent investigations did not confirm those findings.Alveolar IH developing during apnoeic episodes during sleep in OSA patients is a diseaseinduced model to study its effects on pulmonary haemodynamics. In the majority of studies in OSA patients pulmonary arterial pressure remained within normal values. PH was found in patients with OSA accompanied by COPD and/or extreme obesity.People commuting between lowland and high altitude due to their employment, are also repeatedly exposed to IH. Results of clinical investigations suggest that it did not lead to the development of permanent PH.The mechanisms of discrepancies between effects of intermittent hypoxia in animal models and in humans remain to be studied.

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Section: Intermittent Hypoxia In Animal Modelsmentioning

confidence: 99%

Effects of intermittent hypoxia on pulmonary haemodynamics: animal modelsversusstudies in humans

Zieliński¹

2005

Eur Respir J

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“…Among the beneficial effects, there is a recognized cardioprotection with improvement of the myocardial tolerance to ischemic episodes. A number of studies involving exposure to natural (22) or simulated (29) hypobaric hypoxia reported that this adaptation is associated to lower incidence and smaller size of myocardial infarction (30).…”

mentioning

confidence: 99%

Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil,l-NAME, andl-arginine treatments

Zaobornyj¹,

Valdez²,

Iglesias³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Zaobornyj T, Valdez LB, Iglesias DE, Gasco M, Gonzales GF, Boveris A. Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil, L-NAME, and L-arginine treatments. Am J Physiol Heart Circ Physiol 296: H1741-H1747, 2009. First published April 3, 2009 doi:10.1152/ajpheart.00422.2008.-Rats submitted to high altitude (Cerro de Pasco, Perú, 4,340 m, PO2 ϭ 12.2 kPa) for up to 84 days showed a physiological adaptive response with decreased body weight gain (15%), increased right ventricle weight (100%), and increased hematocrit (40%) compared with sea level animals. These classical parameters of adaptation to high altitude were accompanied by an increase in heart mitochondrial enzymes: complexes I-III activity by 34% and mitochondrial nitric oxide synthase (mtNOS) activity and expression by Ͼ75%. The hyperbolic increase for mtNOS activity during adaptation to high altitude was similar to the observed pattern for hematocrit. Hematocrit and mtNOS activity mean values correlated linearly (r 2 ϭ 0.75, P Յ 0.05). Chronic treatment for 28 days with sildenafil (50 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) decreased the response of mtNOS to high altitude by 25%. Conversely, N Gnitro-L-arginine methyl ester treatment (8.3 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) increased such response by 40%, whereas L-arginine treatment (106 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) had no effect. Nitric oxide (NO) production by mtNOS accounts for ϳ49% of total cellular NO production in sea level rats and for ϳ54% in rats exposed to high altitude for 84 days. It is concluded that mtNOS is a substantial source of cardiac NO, a factor in the adaptive response to sustained heart hypoxia that is susceptible to be modified by pharmacological treatments. mitochondrial nitric oxide synthase activity; mitochondrial nitric oxide synthase expression; mitochondrial respiratory complexes; hematocrit; nitro-L-arginine methyl ester HIGH ALTITUDE IS A MULTIFACTORIAL source of stress in which hypobaric hypoxia is the most important component. The O 2 gradient between atmospheric air and cells decreases from 105 mmHg at sea level to 49 mmHg at high altitude (20). There are a number of adaptive responses that are triggered by this situation, such as increased ventilation (28), pulmonary hypertension (40), erythropoiesis (39), and heart work load. The adaptation to high altitude constitutes a situation that has both advantageous and disadvantageous consequences for human health. The main long term effects are decreased physical activity and life span. Among the beneficial effects, there is a recognized cardioprotection with improvement of the myocardial tolerance to ischemic episodes. A number of studies involving exposure to natural (22) or simulated (29) hypobaric hypoxia reported that this adaptation is associated to lower incidence and smaller size of myocardial infarction (30).Although the mechanism by which adaptation to hypoxia has cardioprotective effects remains not elucidated, nitric oxide (NO) has been extensively proposed as one of the molecular messengers inv...

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“…improved cardiac tolerance in the setting of acute no-flow ischemia. This view is supported by observations that the improved tolerance of chronically hypoxic hearts to acute oxygen deprivation is manifested even in nonperfused myocardial preparations (16).…”

Section: Discussionmentioning

confidence: 82%

ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats

Rakusan¹,

Chvojkova²,

Oliviéro³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Rakusan K, Chvojkova Z, Oliviero P, Ostadalova I, Kolar F, Chassagne C, Samuel JL, Ostadal B. ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats. Am J Physiol Heart Circ Physiol 292: H1237-H1244, 2007. First published December 1, 2006; doi:10.1152/ajpheart.00965.2006.-Chronic hypoxia has been shown to stimulate myocardial microvascular growth and improve cardiac ischemic tolerance in young and adult rats. The aim of this study was to determine whether the ANG II type 1 receptor (AT1) pathway was involved in these processes. Newborn Wistar rats, exposed to chronic intermittent hypoxia (8 h/day) for 10 days, were simultaneously treated with AT1 receptor blocker irbesartan and compared with untreated animals. The major finding is that chronic hypoxia increased the capillary supply of myocardial tissue, which was even more pronounced in hypertrophied right ventricle, whereas increased arteriolar supply was found only in the left ventricle. This angiogenic response was completely prevented by irbesartan. Moreover, chronic hypoxia improved the postischemic recovery of cardiac contractile function during reperfusion, and this protective effect was also completely abolished by irbesartan. Chronic hypoxia increased the myocardial density of AT1 but not of ANG II type 2 receptor subtypes, whereas the effect of irbesartan was not significant. The expression of caveolin-1␣ markedly increased in response to chronic hypoxia, and irbesartan prevented this effect. Neither hypoxia nor irbesartan treatment altered the expression of nitric oxide synthase 3, heat shock protein 90, and VEGF. It is concluded that the AT1 receptor pathway plays an important role in coronary angiogenesis and improved cardiac ischemic tolerance induced in neonatal rats by chronic hypoxia.angiotensin II receptors; ischemia-reperfusion; caveolin-1 ADAPTATION TO CHRONIC HYPOXIA increases cardiac tolerance to all major deleterious consequences of acute oxygen deprivation in both adult and immature heart. In addition to the protective effect, chronic hypoxia may also induce other adaptive responses, including hypoxic pulmonary hypertension and right ventricular (RV) hypertrophy (22). This is a beneficial adaptation, allowing the RV to cope with an increased afterload and to maintain cardiac output. Although many potential factors have been proposed to play a role in the mechanisms of cardiac adaptation to chronic hypoxia, the available data are not sufficiently conclusive. Moreover, a substantial amount of information concerning the adaptive response was obtained from the adult myocardium, whereas much less is known about this process in the immature heart. However, clinical relevance of the developmental approach is obvious: chronic hypoxia is the main pathophysiological feature of hypoxemic congenital heart disease. Understanding the mechanisms by which these malformations modify the myocardium and how they impact on the adaptive mechanisms during ischemia may provide ins...

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Physiological responses of rats to intermittent high-altitude stress: effects of age.

Cited by 53 publications

References 0 publications

Effects of intermittent hypoxia on pulmonary haemodynamics: animal modelsversusstudies in humans

Effects of intermittent hypoxia on pulmonary haemodynamics: animal modelsversusstudies in humans

Mitochondrial nitric oxide metabolism during rat heart adaptation to high altitude: effect of sildenafil,l-NAME, andl-arginine treatments

ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats

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