Pulmonary Vasculature of Adult Rats Is Influenced by Perinatal Experience of Hypoxia

Author(s):  
Jan Herget ◽  
V�clav Hampl
2001 ◽  
Vol 91 (2) ◽  
pp. 919-928 ◽  
Author(s):  
Natalie Hopkins ◽  
Elaine Cadogan ◽  
Shay Giles ◽  
Paul McLoughlin

In both pulmonary and systemic hypertension, the walls of the arteriolar vessels are thickened and the lumen size is reduced, leading to increased total vascular resistance. It has been reported previously that chronic airway infection and inflammation lead to increased wall thickness in the pulmonary vasculature, without the development of pulmonary hypertension. The aim of the present study was to examine quantitatively the remodeling of intra-acinar blood vessels in chronically infected rat lungs. Adult rats were anesthetized and inoculated intratracheally with Pseudomonas aeruginosa( n = 10) incorporated into agar beads to induce chronic airway infection. Control groups included rats inoculated with sterile agar beads ( n = 8) and rats that were not inoculated ( n = 6). Chronic infection caused vascular wall thickening without reduction in mean lumen radius. Furthermore, chronic infection led to increased total length of intra-acinar vessels and increased numbers of branch points, demonstrating that angiogenesis had occurred. Preservation of lumen size and formation of new parallel pathways in the vasculature of chronically infected lungs account for the maintenance of normal PVR despite vessel wall remodeling.


1980 ◽  
Vol 238 (5) ◽  
pp. R395-R399 ◽  
Author(s):  
K. B. Wallace ◽  
R. A. Roth ◽  
J. B. Hook ◽  
M. D. Bailie

The pulmonary vasculature has been implicated in the clearance of several vasoactive substances from the circulation including angiotensin I (AI). In view of the previously reported age-related differences in angiotensin-converting enzyme (ACE) activity of lung homogenates, it was of interest to examine the ability of intact perfused lungs to metabolize AI. Lungs from newborn and adult rats were perfused with Krebs bicarbonate buffer containing 1.0 ng/ml AI in a single-pass, nonrecirculating system. The rate of perfusion was normalized to lung mass. Removal of AI was determined from the transpulmonary difference in radioimmunoassayable AI. Lungs from 7-day-old rats removed a smaller fraction of AI from the circulation than did adult lungs. The age-related increase in AI clearance was accompanied by an increase in pulmonary ACE content; however, enzyme content alone could not account for the observed differences. The increased metabolism of AI by the pulmonary vasculature during development may contribute to the age-related increase in circulating angiotensin II concentrations.


1990 ◽  
Vol 68 (3) ◽  
pp. 419-424 ◽  
Author(s):  
T. S. Hakim ◽  
J. P. Mortola

Newborn rats were exposed to hypoxia (10% O2 + N2) from 24 h to day 6 of neonatal life and then returned to room air until 45 days of age (experimental). The rats were anaesthetized, heparinized, and exsanguinated. The chest was opened and the lungs were perfused with diluted autologous blood at a constant flow rate (Q). The pulmonary arterial pressure (Pa) and venous pressure (Pv) were monitored. The properties of the pulmonary vasculature were assessed by measuring baseline vascular resistance, PVR = (Pa−Pv)/Q, segmental pressure gradients (double occlusion technique), pressure–flow relationship, hypoxic pressor response (HPR, 3% O2), and the response to 0.5 μg bolus of angiotensin II (AII). These were compared with similar measurements on age-matched control animals never exposed to hypoxia. The perfusate hematocrit and gases were not significantly different between the two groups. The PVR normalized to body weight was 30% higher in the experimental groups (p < 0.005). The double occlusion results (obtained at a flow rate of 13 mL/min) revealed that this increase in resistance was primarily due to the increase in the postcapillary resistance. HPR was primarily in the upstream segment in both groups but was larger in the experimental group. In contrast, the response to AII occurred in both the upstream as well as in the downstream vascular segments and did not differ between the two groups. We conclude that adult rats exposed to hypoxia in the neonatal period have elevated pulmonary vascular resistance and increased vascular reactivity to hypoxia.Key words: resistance, angiotensin, lung development, pulmonary hypertension.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shanshan Xu ◽  
Xuefeng Xu ◽  
Ziming Zhang ◽  
Lingling Yan ◽  
Liyan Zhang ◽  
...  

Abstract Background Pulmonary hypertension (PH) is a complex pulmonary vascular disease characterized by an imbalance in vasoconstrictor/vasodilator signaling within the pulmonary vasculature. Recent evidence suggests that exposure to hypoxia early in life can cause alterations in the pulmonary vasculature and lead to the development of PH. However, the long-term impact of postnatal hypoxia on lung development and pulmonary function remains unknown. N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of PH remains poorly characterized. Thus, the purpose of this investigation was to test the two-fold hypothesis that (1) postnatal exposure to hypoxia would alter lung development leading to PH in adult rats, and (2) m6A modification would change in rats exposed to hypoxia, suggesting it plays a role in the development of PH. Methods Twenty-four male Sprague–Dawley rats were exposed to a hypoxic environment (FiO2: 12%) within 24 h after birth for 2 weeks. PH was defined as an increased right ventricular pressure (RVP) and pathologic changes of pulmonary vasculature measured by α-SMA immunohistochemical staining. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to analyze m6A modification changes in lung tissue in 2- and 9-week-old rats that were exposed to postnatal hypoxia. Results Mean pulmonary arterial pressure, lung/body weight ratio, and the Fulton index was significantly greater in rats exposed to hypoxia when compared to control and the difference persisted into adulthood. m6A methyltransferase and demethylase proteins were significantly downregulated in postnatal hypoxia-induced PH. Distinct m6A modification peak-related genes differed between the two groups, and these genes were associated with lung development. Conclusions Our results indicate postnatal hypoxia can cause PH, which can persist into adulthood. The development and persistence of PH may be because of the continuous low expression of methyltransferase like 3 affecting the m6A level of PH-related genes. Our findings provide new insights into the impact of postnatal hypoxia and the role of m6A in the development of pulmonary vascular pathophysiology.


2020 ◽  
Author(s):  
shanshan xu ◽  
Xuefeng Xu ◽  
Ziming Zhang ◽  
Lingling Yan ◽  
Liyan Zhang ◽  
...  

Abstract Background: Pulmonary hypertension (PH) is a complex pulmonary vascular disease characterized by an imbalance in vasoconstrictor/vasodilator signaling within the pulmonary vasculature. Recent evidence suggests that exposure to hypoxia early in life can cause alterations in the pulmonary vasculature and lead to the development of PH. However, the long-term impact of postnatal hypoxia on lung development and pulmonary function remains unknown. N6-methyladenosine (m6A) regulates gene expression and governs many important biological processes. However, the function of m6A in the development of PH remains poorly characterized. Thus, the purpose of this investigation was to test the two-fold hypothesis that 1) postnatal exposure to hypoxia would alter lung development leading to PH in adult rats, and 2) m6A modification would change in rats exposed to hypoxia, suggesting it plays a role in the development of PH.Methods: Forty male Sprague-Dawley rats were exposed to a hypoxic environment (FiO2: 12%) within 24 h after birth for 2 weeks. PH was defined as an increased right ventricular systolic pressure (RVSP) and pathologic changes of pulmonary vasculature measured by α-SMA immunohistochemical staining. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) was performed to analyze m6A modification changes in lung tissue between 2 and 9 weeks following exposure to postnatal hypoxia.Results: mean pulmonary arterial pressure, lung/body weight ratio, and the Fulton index was significantly greater in rats exposed to hypoxia when compared to control and the difference persisted into adulthood. m6A methyltransferase and demethylase proteins were significantly downregulated in postnatal hypoxia-induced PH. Distinct m6A modification peak-related genes differed between the two groups, and these genes were associated with lung development.Conclusions: Our results indicate postnatal hypoxia dysregulates lung development, leading to PH, and may have a long-term effect on adult rat lung development via the alterations in pulmonary vasculature function. METTL3, a m6A methyltransferase, was elevated in rats exposed to postnatal hypoxia in both the postnatal period and in adulthood, suggesting that it contributes to the development of PH following postnatal hypoxia. Our findings provide new insights into the impact of postnatal hypoxia and the role of m6A in the development of pulmonary vascular pathophysiology.


1980 ◽  
Vol 239 (5) ◽  
pp. R401-R406
Author(s):  
K. B. Wallace ◽  
M. D. Bailie ◽  
J. B. Hook ◽  
R. A. Roth

The pulmonary vasculature has been implicated in the clearance of several vasoactive peptides, prostaglandins, and biogenic amines from the circulation. In view of the age-related differences in the metabolism of angiotensin by intact lungs, it was of interest to examine the maturation of 5-hydroxytryptamine (5-HT) disposition by isolated perfused lungs. Lungs from newborn and adult rats were perfused with Krebs bicarbonate buffer containing 0.1 microM 5-[14C]HT and samples of the effluent medium collected and analyzed for 5-HT and metabolite. Adult lungs removed and a greater fraction of perfused 5-HT than did lungs from 7-day-old rats. No age-related difference in monoamine oxidase (MAO) activity was observed; however, lung slices from adult rats incubated with 5-[14C]HT accumulated radiolabel at a greater rate than did slices from lungs of 7-day-old rats. The age-related difference in 5-HT clearance by intact lungs may be attributable to a relative deficiency in the facilitated transport process for 5-HT in newborns and may reflect a general functional maturation of processes associated with pulmonary endothelial cell membranes.


Author(s):  
Alfredo Feria-Velasco ◽  
Guadalupe Tapia-Arizmendi

The fine structure of the Harderian gland has been described in some animal species (hamster, rabbit, mouse, domestic fowl and albino rats). There are only two reports in the literature dealing on the ultrastructure of rat Harderian gland in adult animals. In one of them the author describes the myoepithelial cells in methacrylate-embbeded tissue, and the other deals with the maturation of the acinar cells and the formation of the secretory droplets. The aim of the present work is to analize the relationships among the acinar cell components and to describe the two types of cells located at the perifery of the acini.


Author(s):  
Beverly L. Giammara ◽  
Jennifer S. Stevenson ◽  
Peggy E. Yates ◽  
Robert H. Gunderson ◽  
Jacob S. Hanker

An 11mm length of sciatic nerve was removed from 10 anesthetized adult rats and replaced by a biodegradable polyester Vicryl™ mesh sleeve which was then injected with the basement membrane gel, Matrigel™. It was noted that leg sensation and movement were much improved after 30 to 45 days and upon sacrifice nerve reconnection was noted in all animals. Epoxy sections of the repaired nerves were compared with those of the excised segments by the use of a variation of the PAS reaction, the PATS reaction, developed in our laboratories for light and electron microscopy. This microwave-accelerated technique employs periodic acid, thiocarbohydrazide and silver methenamine. It stains basement membrane or Type IV collagen brown and type III collagen (reticulin), axons, Schwann cells, endoneurium and perineurium black. Epoxy sections of repaired and excised nerves were also compared by toluidine blue (tb) staining. Comparison of the sections of control and repaired nerves was done by computer-assisted microscopic image analysis using an Olympus CUE-2 Image Analysis System.


Author(s):  
Tony M. Mosconi ◽  
Min J. Song ◽  
Frank L. Rice

Whiskers or vibrissal follicle-sinus complexes (F-SCs) on the snouts of many mammalian species are structures that have complex, dense sensory innervation. The innervation of F-SCs is remarkably similar in all species with the exception of one site - the inner conical body (ICB). The ICB is an elongated cylindrical structure that encircles the hair shaft near the neck of the follicle. This site has received only cursory attention in ultrastructural studies of the F-SCAdult rats were perfused after the method of Renehan and Munger2. F-SCs were quartered longitudinally and embedded separately in Epon-Araldite. Serial 0.25 μm sections were cut in either the longitudinal or perpendicular plane through the ICB and examined with an AEI EM7 1.2 MV HVEM (Albany, NY) at 1000 KV. Sensory endings were reconstructed from serial micrographs through at least 20 μm in the longitudinal plane and through 10 μm in the perpendicular plane.From two to six small superficial vibrissal nerves converge upon the neck of the F-SC and descend into the ICB. The nerves branch into smaller bundles of myelinated and unmyelinated axons along the dorsal side of the hair shaft.


2019 ◽  
Vol 133 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Nathalie D. Elliott ◽  
Rick Richardson

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