Adventitial Alterations Are the Main Features in Pulmonary Artery Remodeling due to Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats (original) (raw)
Related papers
Annals of Biomedical Engineering, 2000
The remodeling of the pulmonary arterial tissue in response to a step change of the oxygen concentration in the gas in which a rat lives was recorded as function of time and function of O 2 concentration. Three steps of changing from 20.9% to 17.2%, 13.6%, and 10% O 2 were imposed. Earlier work in our laboratory has shown that pulmonary arterial tissue remodeling is significant in the first 24 h after a step change of oxygen tension. Hence we made measurements in this period. Furthermore, data were obtained for tissue remodeling of circumferential and axial lengths of the pulmonary arteries. We recorded the activities of gene expressions in the lung tissues by microarray, determined the dose response curves of gene expression in the homogenized whole lungs with respect to four levels of O 2 concentration, and obtained the time courses of gene expression in the lung parenchyma in 30 days after a step decrease of O 2 concentration from 20.9% to 10%. We would like to suggest that the correlation of gene expression with physiological function parameters, i.e., time, O 2 tension, blood pressure, opening angle, wall thicknesses, etc., is the way to narrow down the search for specific genes for specific physiological functions.
Endothelial cell pavement pattern in the pulmonary trunk in rats in chronic hypoxia
British Journal of Diseases of the Chest, 1980
Right ventricular hypertrophy, and by inference pulmonary arterial hypertension, were induced in female Wistar Albino rats by subjecting them to a barometric pressure of 380 mmHg for four weeks. A control group was kept at normal barometric pressure for a similar period of time. The cell boundaries of the endothelial lining of the aorta, pulmonary trunk and inferior vena cava were stained in situ by a modified silver method of Poole et al. (1958). Photomicrographs of the intimal surfaces of these blood vessels at a standard magnification were used to determine the length, breadth and area of the cells. In the control rats the endothelial cells were found to have a characteristic shape and size in each of the three vessels studied. Those of the aorta were small and elongated in the direction of blood flow with tapering ends. The endothelial cells of the inferior vena cava were rectangular. Those of the pulmonary trunk were polygonal and had tessellated borders. In the test rats with right ventricular hypertrophy induced by chronic hypoxia the endothelial cell pavement pattern of the pulmonary trunk changed to resemble that of the aorta. It is considered that this was an expression of the acquired pulmonary hypertension, the fusiform shape appearing appropriate for an elevated pressure.
Antioxidants, 2021
Chronic sustained hypoxia (CSH), as found in individuals living at a high altitude or in patients suffering respiratory disorders, initiates physiological adaptations such as carotid body stimulation to maintain oxygen levels, but has deleterious effects such as pulmonary hypertension (PH). Obstructive sleep apnea (OSA), a respiratory disorder of increasing prevalence, is characterized by a situation of chronic intermittent hypoxia (CIH). OSA is associated with the development of systemic hypertension and cardiovascular pathologies, due to carotid body and sympathetic overactivation. There is growing evidence that CIH can also compromise the pulmonary circulation, causing pulmonary hypertension in OSA patients and animal models. The aim of this work was to compare hemodynamics, vascular contractility, and L-arginine-NO metabolism in two models of PH in rats, associated with CSH and CIH exposure. We demonstrate that whereas CSH and CIH cause several common effects such as an increase...
The American Journal of the Medical Sciences, 1996
The hypoxic model of pulmonary hypertension was used to examine temporal alterations in the deposition of the basement membrane (BM) and components of fibronectin, laminin, and Type IV collagen within vascular, airway, and gas exchange compartments of the lung. Because hypoxic pulmonary hypertension is a reversible model of hypertension, changes in fibronectin and laminin synthesis/deposition in the recovering lung were also examined. Long-term hypoxic exposure produced decreases in body weight, increased right ventricular and lung dry weights and elevations in pulmonary arterial pressure. Immunohistochemical analysis revealed consistent and progressive increases in the deposition of fibronectin and laminin, but not type IV collagen, in the subendothelial and medial BMs of large and small pulmonary arteries, but not in airways or lung parenchyma. These changes were observed by day 4 of hypoxia and were most prominent in the conducting vasculature. Northern analysis showed a biphasic pattern of alterations in steady-state levels of BM component mRN A in hypoxic rats with early reductions at days 4 and 7 followed by increases at day 12. Recovery from 12 days of hypoxia From the
Chronic hypoxia does not cause wall thickening of intra‐acinar pulmonary supernumerary arteries
Physiological Reports, 2016
Chronic exposure to hypoxia causes pulmonary hypertension and pulmonary arterial remodeling. Although the exact mechanisms of this remodeling are unclear, there is evidence that it is dependent on hemodynamic stress, rather than on hypoxia alone. Pulmonary supernumerary arteries experience low hemodynamic stress as a consequence of reduced perfusion due to 90°b ranching angles, small diameters, and "valve-like" structures at their orifices. We investigated whether or not intra-acinar supernumerary arteries undergo structural remodeling during the moderate pulmonary hypertension induced by chronic hypoxia. Rats were exposed to either normoxia or hypoxia for 6 weeks. The chronically hypoxic rats developed pulmonary hypertension. For both groups, pulmonary arteries were selectively filled with barium-gelatin mixture, and the wall thickness of intra-acinar pulmonary arteries was measured in histological samples. Only thin-walled arteries were observed in normoxic lungs. In hypertensive lungs, we found both thin-and thick-walled pulmonary arteries with similar diameters. Disproportionate degrees of arterial wall thickening between parent and daughter branches were observed with supernumerary branching patterns. While parent arteries developed significant wall thickening, their supernumerary branches did not. Thus, chronic hypoxia-induced pulmonary hypertension did not cause wall thickening of intra-acinar pulmonary supernumerary arteries. These findings are consistent with the idea that hemodynamic stress, rather than hypoxia alone, is the cause of structural remodeling during chronic exposure to hypoxia.
Recovery from hypoxic pulmonary hypertension in rats
Acta medica (Hradec Králové) / Universitas Carolina, Facultas Medica Hradec Králové, 2011
To characterize the time frame of changes in pulmonary arterial pressure, right ventricular hypertrophy and morphology of small pulmonary arteries male Wistar rats were exposed to isobaric hypoxia (3 weeks, F1O2 0.1) and then let to recover on air for 1 or 5 weeks. Normoxic animals (group N) served as controls. Mean pulmonary arterial pressure (PAP), ratio of the weight of the right heart ventricle to the sum of the weights of the left ventricle and septum (RV/LV+S) and percentage of double laminated pulmonary vessels ( % DL) were measured at the end of hypoxic exposure (group H), after 1 or 5 weeks of recovery (groups 1R and 5R), and in controls kept in air (group N). Three weeks in hypoxia resulted in increase in PAP, RV/LV+S and % DL. After 1 week of recovery RV/LV+S normalized, PAP decreased, while % DL did not change. After 5 weeks in air PAP returned to control values and % DL diminished significantly but did not normalize. Our results suggest that recovery depends on the degr...
AJP: Heart and Circulatory Physiology, 2007
Excessive proliferation of vascular wall cells underlies the development of elevated vascular resistance in hypoxic pulmonary hypertension (PH), but the responsible mechanisms remain unclear. Growth-promoting effects of catecholamines may contribute. Hypoxemia causes sympatho-excitation, and prolonged stimulation of 1 -adrenoceptors induces hypertrophy and hyperplasia of arterial smooth muscle cells and adventitial fibroblasts. Catecholamine trophic actions in arteries are enhanced when other conditions favoring growth or remodeling are present, eg injury, altered shear stress and, notably, in isolated pulmonary arteries from rats with hypoxic PH. The present study examined the hypothesis that catecholamines contribute to pulmonary vascular remodeling in vivo in hypoxic PH. Mice genetically deficient in norepinephrine and epinephrine production (dopamine -hydroxylase -/-, DBH -/-) or 1 -adrenoceptors were examined for alterations in PH, cardiac hypertrophy and vascular remodeling after 21 days exposure to normobaric 0.1 FIO 2 . Decrease in lumen area and increase in wall thickness of arteries were strongly inhibited in knockout mice (order of extent of inhibition: D H -/-= 1D -AR -/-> 1B -AR -/-). Distal muscularization of small arterioles was also reduced (D H -/-> 1D -AR -/-> 1B -AR -/mice). Despite these reductions, increases in right ventricular pressure and hypertrophy were not attenuated in D H -/and 1B -AR -/-
Open Journal of Molecular and Integrative Physiology, 2012
Pulmonary diseases associated with diurnal hypoxemia are known to be associated with pulmonary hypertension in some patients. In this study we examined the effects of daily hypoxia (10% oxygen; 8h/day for 14 days) on two strains of rats to simulate sleep related hypoxia in pulmonary diseases expecting to find differences in vascular responses, the development of right ventricular hypertrophy and pulmonary hypertension according to genetic background. In response to daily hypoxia, Sprague Dawley rats developed right ventricular hypertrophy while Brown Norway rats did not. Both strains developed pulmonary hypertension (elevated right ventricular pressure) although the increase was significantly greater in the Sprague Dawley strain. Pulmonary artery (first branch) vasoconstrictive responses to potassium chloride were increased equally in both strains and the subsequent vasodilation with acetylcholine were reduced equally with daily hypoxia in both strains. Taken together, these findings suggest that the genetic makeup of the rats contributed significantly to the development of right ventricular hypertrophy and the degree of pulmonary hypertension. Moreover, this response is not secondary to differences in the intralobar pulmonary vascular reactivity. Genetic background could explain why certain patients do worse with hypoxia inducing pulmonary vascular diseases.
Endothelial ETB Limits Vascular Remodelling and Development of Pulmonary Hypertension during Hypoxia
Journal of Vascular Research, 2010
Background: We hypothesised that the potential protective effects of endothelial ETB are important in limiting pulmonary vascular muscularisation, vasoconstriction and the development of pulmonary arterial hypertension in response to hypoxia. Methods: EC-specific ETB knockout mice (EC ETB–/–) and control mice (ETBf/f) were subjected to hypobaric hypoxic (10% FiO2) or normoxic conditions for 14 days before assessment of right ventricular pressure and pulmonary vascular morphology and function. Results: During normoxia, no difference in right ventricular pressure was detected between EC ETB–/– (23.7 ± 1.7 mm Hg) and ETBf/f mice (20.2 ± 1.5 mm Hg). Hypoxia induced an exaggerated increase in right ventricular pressure in EC ETB–/– mice (34.4 ± 1.2 mm Hg vs. 24.6 ± 1.4 mm Hg), accompanied by an increase in right ventricular mass. No effect was observed in ETBf/f mice. Endothelin-1 constricted pulmonary arteries from both groups, although maximum response was similar irrespective of inspi...