Chronic hypoxic pulmonary hypertension in rats and increased elastolytic activity
K. Maruyama, C. L. Ye, M. Woo, H. Venkatacharya, L. D. Lines, M. M. Silver and M. Rabinovitch Department of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada. Previously in rats injected with the toxin monocrotaline and administered SC-39026, a serine elastase inhibitor, pulmonary hyp...
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creator | Maruyama, K Ye, C. L Woo, M Venkatacharya, H Lines, L. D Silver, M. M Rabinovitch, M |
description | K. Maruyama, C. L. Ye, M. Woo, H. Venkatacharya, L. D. Lines, M. M. Silver and M. Rabinovitch
Department of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada.
Previously in rats injected with the toxin monocrotaline and administered
SC-39026, a serine elastase inhibitor, pulmonary hypertension was decreased
in association with reduced muscularization of peripheral pulmonary
arteries. To determine whether inhibition of elastolytic activity might
prevent this vascular change in other conditions producing pulmonary
hypertension, we administered SC-39026 to rats during a 10-day exposure to
chronic hypobaric hypoxia. We also measured elastolytic activity in the
central pulmonary arteries of rats using [3H]elastin substrate and
determined whether there was an increase in activity either as early as 2
days or at completion of the hypoxic exposure, which could be inhibited by
SC-39026. to further determine whether the mechanism of muscularization of
peripheral arteries is modulated by degradation of elastin or other
elastase-susceptible extracellular matrix proteins, we assessed desmosine
excretion and ultrastructural alterations in elastin as well as in type IV
collagen, fibronectin, and laminin. SC-39026 reduced the number of
muscularized arteries and the level of pulmonary arterial pressure during
exposure to chronic hypoxia. Elastolytic activity was fourfold higher in
central pulmonary arteries 2 days after hypoxia when compared with values
in control vessels, and the activity was inhibited by SC-39026. In small
peripheral pulmonary arteries there were no significant changes with
hypoxia reflected in desmosines or in the immunocytochemistry of
elastase-susceptible glycoproteins, with the exception of decreased
laminin. This feature was not inhibited by SC-39026. To further assess
whether the protective effect of SC-39026 was related to its inhibition of
elastase, an extended study was carried out using a different elastase
inhibitor, alpha 1-proteinase inhibitor. An even greater reduction in
hypoxia-induced pulmonary hypertension and vascular changes was observed
with this elastase inhibitor and the latter included medial hypertrophy. |
doi_str_mv | 10.1152/ajpheart.1991.261.6.h1716 |
format | Article |
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Department of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada.
Previously in rats injected with the toxin monocrotaline and administered
SC-39026, a serine elastase inhibitor, pulmonary hypertension was decreased
in association with reduced muscularization of peripheral pulmonary
arteries. To determine whether inhibition of elastolytic activity might
prevent this vascular change in other conditions producing pulmonary
hypertension, we administered SC-39026 to rats during a 10-day exposure to
chronic hypobaric hypoxia. We also measured elastolytic activity in the
central pulmonary arteries of rats using [3H]elastin substrate and
determined whether there was an increase in activity either as early as 2
days or at completion of the hypoxic exposure, which could be inhibited by
SC-39026. to further determine whether the mechanism of muscularization of
peripheral arteries is modulated by degradation of elastin or other
elastase-susceptible extracellular matrix proteins, we assessed desmosine
excretion and ultrastructural alterations in elastin as well as in type IV
collagen, fibronectin, and laminin. SC-39026 reduced the number of
muscularized arteries and the level of pulmonary arterial pressure during
exposure to chronic hypoxia. Elastolytic activity was fourfold higher in
central pulmonary arteries 2 days after hypoxia when compared with values
in control vessels, and the activity was inhibited by SC-39026. In small
peripheral pulmonary arteries there were no significant changes with
hypoxia reflected in desmosines or in the immunocytochemistry of
elastase-susceptible glycoproteins, with the exception of decreased
laminin. This feature was not inhibited by SC-39026. To further assess
whether the protective effect of SC-39026 was related to its inhibition of
elastase, an extended study was carried out using a different elastase
inhibitor, alpha 1-proteinase inhibitor. An even greater reduction in
hypoxia-induced pulmonary hypertension and vascular changes was observed
with this elastase inhibitor and the latter included medial hypertrophy.</description><identifier>ISSN: 0363-6135</identifier><identifier>ISSN: 0002-9513</identifier><identifier>EISSN: 1522-1539</identifier><identifier>DOI: 10.1152/ajpheart.1991.261.6.h1716</identifier><identifier>PMID: 1836309</identifier><language>eng</language><publisher>United States</publisher><subject>alpha 1-Antitrypsin - pharmacology ; Animals ; Cardiomegaly - etiology ; Chlorobenzoates - pharmacology ; Collagen - metabolism ; Elastic Tissue - physiopathology ; Elastin - metabolism ; Fibronectins - metabolism ; Hemodynamics ; Hypertension, Pulmonary - etiology ; Hypertension, Pulmonary - pathology ; Hypertension, Pulmonary - physiopathology ; Hypoxia - complications ; Immunohistochemistry ; Laminin - metabolism ; Male ; Microscopy, Electron ; Pancreatic Elastase - antagonists & inhibitors ; Pulmonary Artery - pathology ; Pulmonary Artery - physiopathology ; Rats ; Rats, Inbred Strains</subject><ispartof>American journal of physiology. Heart and circulatory physiology, 1991-12, Vol.261 (6), p.H1716-H1726</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-88b18a5c709fb15df5fe12f1f29ecb25b7df88c27dbf6dedf1745f57e626d9523</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1836309$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maruyama, K</creatorcontrib><creatorcontrib>Ye, C. L</creatorcontrib><creatorcontrib>Woo, M</creatorcontrib><creatorcontrib>Venkatacharya, H</creatorcontrib><creatorcontrib>Lines, L. D</creatorcontrib><creatorcontrib>Silver, M. M</creatorcontrib><creatorcontrib>Rabinovitch, M</creatorcontrib><title>Chronic hypoxic pulmonary hypertension in rats and increased elastolytic activity</title><title>American journal of physiology. Heart and circulatory physiology</title><addtitle>Am J Physiol</addtitle><description>K. Maruyama, C. L. Ye, M. Woo, H. Venkatacharya, L. D. Lines, M. M. Silver and M. Rabinovitch
Department of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada.
Previously in rats injected with the toxin monocrotaline and administered
SC-39026, a serine elastase inhibitor, pulmonary hypertension was decreased
in association with reduced muscularization of peripheral pulmonary
arteries. To determine whether inhibition of elastolytic activity might
prevent this vascular change in other conditions producing pulmonary
hypertension, we administered SC-39026 to rats during a 10-day exposure to
chronic hypobaric hypoxia. We also measured elastolytic activity in the
central pulmonary arteries of rats using [3H]elastin substrate and
determined whether there was an increase in activity either as early as 2
days or at completion of the hypoxic exposure, which could be inhibited by
SC-39026. to further determine whether the mechanism of muscularization of
peripheral arteries is modulated by degradation of elastin or other
elastase-susceptible extracellular matrix proteins, we assessed desmosine
excretion and ultrastructural alterations in elastin as well as in type IV
collagen, fibronectin, and laminin. SC-39026 reduced the number of
muscularized arteries and the level of pulmonary arterial pressure during
exposure to chronic hypoxia. Elastolytic activity was fourfold higher in
central pulmonary arteries 2 days after hypoxia when compared with values
in control vessels, and the activity was inhibited by SC-39026. In small
peripheral pulmonary arteries there were no significant changes with
hypoxia reflected in desmosines or in the immunocytochemistry of
elastase-susceptible glycoproteins, with the exception of decreased
laminin. This feature was not inhibited by SC-39026. To further assess
whether the protective effect of SC-39026 was related to its inhibition of
elastase, an extended study was carried out using a different elastase
inhibitor, alpha 1-proteinase inhibitor. An even greater reduction in
hypoxia-induced pulmonary hypertension and vascular changes was observed
with this elastase inhibitor and the latter included medial hypertrophy.</description><subject>alpha 1-Antitrypsin - pharmacology</subject><subject>Animals</subject><subject>Cardiomegaly - etiology</subject><subject>Chlorobenzoates - pharmacology</subject><subject>Collagen - metabolism</subject><subject>Elastic Tissue - physiopathology</subject><subject>Elastin - metabolism</subject><subject>Fibronectins - metabolism</subject><subject>Hemodynamics</subject><subject>Hypertension, Pulmonary - etiology</subject><subject>Hypertension, Pulmonary - pathology</subject><subject>Hypertension, Pulmonary - physiopathology</subject><subject>Hypoxia - complications</subject><subject>Immunohistochemistry</subject><subject>Laminin - metabolism</subject><subject>Male</subject><subject>Microscopy, Electron</subject><subject>Pancreatic Elastase - antagonists & inhibitors</subject><subject>Pulmonary Artery - pathology</subject><subject>Pulmonary Artery - physiopathology</subject><subject>Rats</subject><subject>Rats, Inbred Strains</subject><issn>0363-6135</issn><issn>0002-9513</issn><issn>1522-1539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkEFr3DAQhUVp2G6S_oSCe-nNjkdeydaxLG0SCIRAchayNForeC1X0rbxv6-WTUhOM8yb94b5CPkOdQXA6JV6ngdUIVUgBFSUQ8WrAVrgn8g667QE1ojPZF03vCk5NOwLOY_xua5r1vJmRVbQZaUWa_KwHYKfnC6GZfYvuc6Hce8nFZbjBEPCKTo_FW4qgkqxUJPJvQ6oIpoCRxWTH5eUjUon99el5ZKcWTVG_PpaL8jT71-P25vy7v76dvvzrtQb6FLZdT10ium2FrYHZiyzCNSCpQJ1T1nfGtt1mramt9ygsdBumGUtcsqNYLS5ID9OuXPwfw4Yk9y7qHEc1YT-EGVLGd9QwfOiOC3q4GMMaOUc3D5_KKGWR5zyDac84pQZp-Ty5ogze7-9Hjn0ezTvzhO_rF-d9MHthn8uoJyHJQMb_W55j_2Y-B-kE4dF</recordid><startdate>19911201</startdate><enddate>19911201</enddate><creator>Maruyama, K</creator><creator>Ye, C. L</creator><creator>Woo, M</creator><creator>Venkatacharya, H</creator><creator>Lines, L. D</creator><creator>Silver, M. M</creator><creator>Rabinovitch, M</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19911201</creationdate><title>Chronic hypoxic pulmonary hypertension in rats and increased elastolytic activity</title><author>Maruyama, K ; Ye, C. L ; Woo, M ; Venkatacharya, H ; Lines, L. D ; Silver, M. M ; Rabinovitch, M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-88b18a5c709fb15df5fe12f1f29ecb25b7df88c27dbf6dedf1745f57e626d9523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>alpha 1-Antitrypsin - pharmacology</topic><topic>Animals</topic><topic>Cardiomegaly - etiology</topic><topic>Chlorobenzoates - pharmacology</topic><topic>Collagen - metabolism</topic><topic>Elastic Tissue - physiopathology</topic><topic>Elastin - metabolism</topic><topic>Fibronectins - metabolism</topic><topic>Hemodynamics</topic><topic>Hypertension, Pulmonary - etiology</topic><topic>Hypertension, Pulmonary - pathology</topic><topic>Hypertension, Pulmonary - physiopathology</topic><topic>Hypoxia - complications</topic><topic>Immunohistochemistry</topic><topic>Laminin - metabolism</topic><topic>Male</topic><topic>Microscopy, Electron</topic><topic>Pancreatic Elastase - antagonists & inhibitors</topic><topic>Pulmonary Artery - pathology</topic><topic>Pulmonary Artery - physiopathology</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maruyama, K</creatorcontrib><creatorcontrib>Ye, C. L</creatorcontrib><creatorcontrib>Woo, M</creatorcontrib><creatorcontrib>Venkatacharya, H</creatorcontrib><creatorcontrib>Lines, L. D</creatorcontrib><creatorcontrib>Silver, M. M</creatorcontrib><creatorcontrib>Rabinovitch, M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maruyama, K</au><au>Ye, C. L</au><au>Woo, M</au><au>Venkatacharya, H</au><au>Lines, L. D</au><au>Silver, M. M</au><au>Rabinovitch, M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronic hypoxic pulmonary hypertension in rats and increased elastolytic activity</atitle><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle><addtitle>Am J Physiol</addtitle><date>1991-12-01</date><risdate>1991</risdate><volume>261</volume><issue>6</issue><spage>H1716</spage><epage>H1726</epage><pages>H1716-H1726</pages><issn>0363-6135</issn><issn>0002-9513</issn><eissn>1522-1539</eissn><abstract>K. Maruyama, C. L. Ye, M. Woo, H. Venkatacharya, L. D. Lines, M. M. Silver and M. Rabinovitch
Department of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada.
Previously in rats injected with the toxin monocrotaline and administered
SC-39026, a serine elastase inhibitor, pulmonary hypertension was decreased
in association with reduced muscularization of peripheral pulmonary
arteries. To determine whether inhibition of elastolytic activity might
prevent this vascular change in other conditions producing pulmonary
hypertension, we administered SC-39026 to rats during a 10-day exposure to
chronic hypobaric hypoxia. We also measured elastolytic activity in the
central pulmonary arteries of rats using [3H]elastin substrate and
determined whether there was an increase in activity either as early as 2
days or at completion of the hypoxic exposure, which could be inhibited by
SC-39026. to further determine whether the mechanism of muscularization of
peripheral arteries is modulated by degradation of elastin or other
elastase-susceptible extracellular matrix proteins, we assessed desmosine
excretion and ultrastructural alterations in elastin as well as in type IV
collagen, fibronectin, and laminin. SC-39026 reduced the number of
muscularized arteries and the level of pulmonary arterial pressure during
exposure to chronic hypoxia. Elastolytic activity was fourfold higher in
central pulmonary arteries 2 days after hypoxia when compared with values
in control vessels, and the activity was inhibited by SC-39026. In small
peripheral pulmonary arteries there were no significant changes with
hypoxia reflected in desmosines or in the immunocytochemistry of
elastase-susceptible glycoproteins, with the exception of decreased
laminin. This feature was not inhibited by SC-39026. To further assess
whether the protective effect of SC-39026 was related to its inhibition of
elastase, an extended study was carried out using a different elastase
inhibitor, alpha 1-proteinase inhibitor. An even greater reduction in
hypoxia-induced pulmonary hypertension and vascular changes was observed
with this elastase inhibitor and the latter included medial hypertrophy.</abstract><cop>United States</cop><pmid>1836309</pmid><doi>10.1152/ajpheart.1991.261.6.h1716</doi></addata></record> |
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ispartof | American journal of physiology. Heart and circulatory physiology, 1991-12, Vol.261 (6), p.H1716-H1726 |
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language | eng |
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source | MEDLINE; Alma/SFX Local Collection |
subjects | alpha 1-Antitrypsin - pharmacology Animals Cardiomegaly - etiology Chlorobenzoates - pharmacology Collagen - metabolism Elastic Tissue - physiopathology Elastin - metabolism Fibronectins - metabolism Hemodynamics Hypertension, Pulmonary - etiology Hypertension, Pulmonary - pathology Hypertension, Pulmonary - physiopathology Hypoxia - complications Immunohistochemistry Laminin - metabolism Male Microscopy, Electron Pancreatic Elastase - antagonists & inhibitors Pulmonary Artery - pathology Pulmonary Artery - physiopathology Rats Rats, Inbred Strains |
title | Chronic hypoxic pulmonary hypertension in rats and increased elastolytic activity |
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