High altitude simulation, substance P and airway rapidly adapting receptor activity in rabbits

Bhagat, Rajesh; Andrabi, Yasir; Vashisht, Anmol; Kulshreshtha, Ritu; Singh, Shashi Bala; Ravindran, Krishnan

doi:10.1016/j.resp.2011.07.005

Cited by 6 publications

(7 citation statements)

References 33 publications

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“…Previous studies have documented that, out of two mountain climbers one develops the signs and symptoms of HAPE with the drastic changes in lung histology [73]. Similar reports were also presented in studies carried out on lung tissues of rats exposed to reducing environment, which demonstrated the fluid build-up, alveolar thickening and pulmonary edema in the lungs [74,75]. Simultaneously, the biochemical findings were further confirmed by histopathological examination of lung sections of control and hypoxia exposed animals.…”

Section: Discussionsupporting

confidence: 68%

Prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats

2019

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The objective of the study was to find out the prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats. Male SD rats received different doses of quercetin @ 25mg, 50mg, 100mg and 200mg/Kg BW, 1h prior to hypobaric hypoxia exposure (7,620m, for 6h). Quercetin 50 mg/kg BW supplemented orally 1h prior to hypoxia exposure was considered to be the optimum dose, due to significant reduction (p<0.001) in lung water content and lung transvascular leakage compared to control (hypoxia, 6h). Further, biochemical analysis (ROS, MDA, GSH, GPx, LDH, and albumin) and differential expressions of proteins (IKK-α/β, NFĸB, Nrf-2,TNF-α, ICAM-1, VCAM, P-selectin, Hif-1α, VEGF, TNF-α, TGF-β, INF-γ and IL-4) were determined by western blotting and ELISA. Changes in lung parenchyma were assessed by histopathology. Quercetin (50 mg/kg BW) prophylaxis under hypoxia showed significant reduction in oxidative stress (ROS and MDA), concomitant increase in antioxidants (GSH, GPx and SOD) followed by decreased LDH and albumin extravasation in BAL fluid over hypoxia. Quercetin prophylaxis significantly down regulated hypoxia induced increase in IKKα/β and NFĸB expressions leading to reduction in the levels of pro-inflammatory cytokines (TNF-α and INF-γ) followed by up regulation of anti-inflammatory cytokines (IL-4 and INF-γ) in lungs. Further, hypoxia mediated increase in HIF-1α was stabilized and VEGF levels in lungs were significantly down regulated by quercetin supplementation, leading to reduction in vascular leakage in lungs of rats under hypoxia. However, Quercetin has also enacted as Nrf-2 activator which significantly boosted up the synthesis of GSH under hypoxic condition compared to hypoxia. Histopathological observations further confirmed that quercetin preconditioning has an inhibitory effect on progression of oxidative stress and inflammation via attenuation of NFκB and stabilization HIF-1α in lungs of rats under hypoxia.These studies indicated that quercetin prophylaxis abrogates the possibility of hypobaric hypoxia induced pulmonary edema in rats.

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Section: Discussionsupporting

confidence: 68%

Prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats

2019

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“…On the sixth day starting from the day of surgery, rats from Groups-Ic, Id, Groups-IIc, IId and Group-IIId were exposed to hypobaric hypoxia for 24 h in a specially designed decompression chamber (Bhagat et al, 2011) which enables the reduction of the barometric pressure, and modulation of temperature and relative humidity; and they were maintained at 294.4 mmHg (equivalent to 7315 m), 25 • C and 55-60%, respectively (Berg et al, 2004). The animals were provided with food and water when exposed in decompression chamber.…”

Section: Exposure To Hypobaric Hypoxiamentioning

confidence: 99%

“…In hypobaric hypoxia exposed animals, the inspired air during experiments was supplemented with 10% O 2 and 90% N 2 . The ventilation was adjusted in such a way that blood gases and pH remained in the same range recorded at the start (Bhagat et al, 2011). The left venous catheter was used for giving maintenance doses of the anesthetic and/or infusions.…”

Section: Cannulation and Ventilation Proceduresmentioning

confidence: 99%

Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema

Sharma

Choudhary

Reddy

et al. 2015

Respiratory Physiology & Neurobiology

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“…However, pulmonary receptors and their role in limiting maximum heart rate in severe hypoxia are still not yet well understood (Widdicombe, 2009). In rabbits basal rapid adapting pulmonary receptor (RAR) activity increases during prolonged exposure to hypoxia accompanied by pulmonary congestion (Bhagat et al, 2011). In humans, exposure to high altitude is accompanied by pulmonary congestion and subclinical interstitial pulmonary edema (Anholm et al, 1999;Cremona et al, 2002).…”

Section: Furosemidementioning

confidence: 99%

“…Another possible explanation for the observed decrease in lower peak heart and cardiac output in lowlanders exercising in severe hypoxia is increased parasympathetic activity (Boushel et al, 2001). A potential origin for increased parasympathetic activity is activation of pulmonary vagal afferents caused by subclinical interstitial pulmonary oedema from hypoxia and exercise-induced increased PAP (Anholm, Milne, Stark, Bourne, & Friedman, 1999;Bhagat et al, 2011;Cremona et al, 2002;Lee & Pisarri, 2001;Paton, 1998). Inhaled furosemide alleviates dyspnoea and improves endurance exercise performance under certain pathological conditions, possibly through pulmonary vagal afferent inhibition (Jensen, Amjadi, Harris-McAllister, Webb, & O'Donnell, 2008;Newton, Davidson, Macdonald, Ollerton, & Krum, 2008;Parshall et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Iloprost improves running performance at 5,000 m in Han but not in Tibetans

Kayser

Fan

2019

CISS

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Background: Tibetans experience lose less aerobic exercise capacity in hypoxia compared to lowland Han. We tested if inhalation of iloprost (to counter hypoxic pulmonary vasoconstriction) and furosemide (to decrease afferent vagal traffic from pulmonary receptors) improve performance in hypoxia in Han compared to Tibetans. Methods: 8 Tibetans and 8 Han, living at 2,260 m, did incremental uphill treadmill running to exhaustion at ambient pressure on day 1, followed by three runs at 5,000 m (hypobaric chamber) after inhalation of iloprost (ILO), furosemide (FUR) or placebo (PLA), on different days in a counter-balanced order. Results: In Han the performance decrement from 2,260 m to 5,000 m was greater than in Tibetans (p<0.05). In Han iloprost improved performance at 5,000 m compared to placebo (p<0.05 vs. PLA); furosemide had no effects. In Tibetans there were no treatment effects. Peripheral O2saturations at peak exercise at 5,000 m, were higher by ～8 % in the Tibetans (p<0.05 vs. Han). Maximum heart rate was lowered by 13±6 bpm in Han at 5,000 m regardless of treatment compared to 2,260 m (p<0.05). Tibetans reached similar maximum heart rates ∼200 bpmat 5,000 m and 2,260 m, independent of treatment. Conclusions: The blunting of the exercise impairment in severe hypoxia in Han during maximal exercise after inhalation of iloprost suggests that hypoxic pulmonary vasoconstriction and right ventricular function are potential performance limiting factors in Han in hypoxia.

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High altitude simulation, substance P and airway rapidly adapting receptor activity in rabbits

Cited by 6 publications

References 33 publications

Prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats

Prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats

Role of posterior hypothalamus in hypobaric hypoxia induced pulmonary edema

Iloprost improves running performance at 5,000 m in Han but not in Tibetans

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