Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide
Carbon monoxide (CO), like nitric oxide (NO), stimulates soluble guanylyl cyclase and thereby raises intracellular levels of cGMP. We examined the endogenous capacity of vascular smooth muscle cells (SMCs) to produce CO from heme through the activity of heme oxygenases. Cultured SMCs from rat aorta...
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Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 1995-05, Vol.91 (9), p.2306-2309 |
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creator | CHRISTODOULIDES, N DURANTE, W KROLL, M. H SCHAFER, A. I |
description | Carbon monoxide (CO), like nitric oxide (NO), stimulates soluble guanylyl cyclase and thereby raises intracellular levels of cGMP. We examined the endogenous capacity of vascular smooth muscle cells (SMCs) to produce CO from heme through the activity of heme oxygenases.
Cultured SMCs from rat aorta (RASMCs) expressed immunoreactive inducible heme oxygenase-1 (HO-1) and constitutive HO-2. Treatment of RASMCs with hemin and sodium arsenite, which are inducers of HO-1, stimulated RASMC cGMP without stimulating nitrite release or inducible NO synthase expression, and the induced elevations of cGMP were not inhibited by the NO synthase inhibitor NG-methyl-L-arginine. Induced CO from RASMCs likewise caused elevation of cGMP levels in platelets coincubated with the vascular cells. Zinc protoporphyrin IX, an inhibitor of HO, reversed the inducible increases in platelet cGMP.
These results indicate that vascular SMCs have both constitutive and inducible HO activity, and they respond to specific stimuli to generate guanylyl cyclase-stimulatory CO in the same SMCs and in coincubated platelets. |
doi_str_mv | 10.1161/01.cir.91.9.2306 |
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Cultured SMCs from rat aorta (RASMCs) expressed immunoreactive inducible heme oxygenase-1 (HO-1) and constitutive HO-2. Treatment of RASMCs with hemin and sodium arsenite, which are inducers of HO-1, stimulated RASMC cGMP without stimulating nitrite release or inducible NO synthase expression, and the induced elevations of cGMP were not inhibited by the NO synthase inhibitor NG-methyl-L-arginine. Induced CO from RASMCs likewise caused elevation of cGMP levels in platelets coincubated with the vascular cells. Zinc protoporphyrin IX, an inhibitor of HO, reversed the inducible increases in platelet cGMP.
These results indicate that vascular SMCs have both constitutive and inducible HO activity, and they respond to specific stimuli to generate guanylyl cyclase-stimulatory CO in the same SMCs and in coincubated platelets.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.cir.91.9.2306</identifier><identifier>PMID: 7729015</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Animals ; Aorta - metabolism ; Arsenites - pharmacology ; Biological and medical sciences ; Blood Platelets - drug effects ; Blood Platelets - metabolism ; Blood vessels and receptors ; Blotting, Western ; Carbon Monoxide - metabolism ; Cells, Cultured ; Culture Media, Conditioned ; Fundamental and applied biological sciences. Psychology ; Guanylate Cyclase - biosynthesis ; Guanylate Cyclase - metabolism ; Heme - metabolism ; Heme Oxygenase (Decyclizing) - analysis ; Hemin - pharmacology ; Muscle, Smooth, Vascular - metabolism ; Rats ; Sodium Compounds - pharmacology ; Vertebrates: cardiovascular system</subject><ispartof>Circulation (New York, N.Y.), 1995-05, Vol.91 (9), p.2306-2309</ispartof><rights>1995 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. May 1, 1995</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-b1228c1963d8c79e8edc0e9cb730f4096498e010295123389ce4782ce20b5df23</citedby><cites>FETCH-LOGICAL-c504t-b1228c1963d8c79e8edc0e9cb730f4096498e010295123389ce4782ce20b5df23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3673,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3522499$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7729015$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHRISTODOULIDES, N</creatorcontrib><creatorcontrib>DURANTE, W</creatorcontrib><creatorcontrib>KROLL, M. H</creatorcontrib><creatorcontrib>SCHAFER, A. I</creatorcontrib><title>Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Carbon monoxide (CO), like nitric oxide (NO), stimulates soluble guanylyl cyclase and thereby raises intracellular levels of cGMP. We examined the endogenous capacity of vascular smooth muscle cells (SMCs) to produce CO from heme through the activity of heme oxygenases.
Cultured SMCs from rat aorta (RASMCs) expressed immunoreactive inducible heme oxygenase-1 (HO-1) and constitutive HO-2. Treatment of RASMCs with hemin and sodium arsenite, which are inducers of HO-1, stimulated RASMC cGMP without stimulating nitrite release or inducible NO synthase expression, and the induced elevations of cGMP were not inhibited by the NO synthase inhibitor NG-methyl-L-arginine. Induced CO from RASMCs likewise caused elevation of cGMP levels in platelets coincubated with the vascular cells. Zinc protoporphyrin IX, an inhibitor of HO, reversed the inducible increases in platelet cGMP.
These results indicate that vascular SMCs have both constitutive and inducible HO activity, and they respond to specific stimuli to generate guanylyl cyclase-stimulatory CO in the same SMCs and in coincubated platelets.</description><subject>Animals</subject><subject>Aorta - metabolism</subject><subject>Arsenites - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood Platelets - drug effects</subject><subject>Blood Platelets - metabolism</subject><subject>Blood vessels and receptors</subject><subject>Blotting, Western</subject><subject>Carbon Monoxide - metabolism</subject><subject>Cells, Cultured</subject><subject>Culture Media, Conditioned</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Guanylate Cyclase - biosynthesis</subject><subject>Guanylate Cyclase - metabolism</subject><subject>Heme - metabolism</subject><subject>Heme Oxygenase (Decyclizing) - analysis</subject><subject>Hemin - pharmacology</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Rats</subject><subject>Sodium Compounds - pharmacology</subject><subject>Vertebrates: cardiovascular system</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkN2L1TAQxYMo63X13RchiPjWmpn0ax7l4sfCgiDqa0jT6W6XtFmTFrb_vbnsZR98Gobzm8OcI8RbUCVAA58UlG6KJUFJJWrVPBMHqLEqqlrTc3FQSlHRasSX4lVKd3ltdFtfiIu2RVJQH4T9Y5PbvI0yzSGst3LekvMsHXsvb3lmGR72G15s4iTz5GhXljebXXa_e-l257NUpHWas8sa4i6djX1Y5ByW8DAN_Fq8GK1P_OY8L8Xvr19-Hb8X1z--XR0_XxeuVtVa9IDYOaBGD51riTsenGJyfavVWClqKupYgUKqAbXuyHHVdugYVV8PI-pL8fHR9z6Gvxun1cxTOsWwC4ctmRxZA3VNBt__B96FLS75N4OAje40niD1CLkYUoo8mvs4zTbuBpQ5VW8UmOPVT0NgyJyqzyfvzr5bP_PwdHDuOusfznqu3Pox2sVN6QnTNWJFpP8BlTmMjg</recordid><startdate>19950501</startdate><enddate>19950501</enddate><creator>CHRISTODOULIDES, N</creator><creator>DURANTE, W</creator><creator>KROLL, M. H</creator><creator>SCHAFER, A. I</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</scope><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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>19950501</creationdate><title>Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide</title><author>CHRISTODOULIDES, N ; DURANTE, W ; KROLL, M. H ; SCHAFER, A. I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-b1228c1963d8c79e8edc0e9cb730f4096498e010295123389ce4782ce20b5df23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>Aorta - metabolism</topic><topic>Arsenites - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood Platelets - drug effects</topic><topic>Blood Platelets - metabolism</topic><topic>Blood vessels and receptors</topic><topic>Blotting, Western</topic><topic>Carbon Monoxide - metabolism</topic><topic>Cells, Cultured</topic><topic>Culture Media, Conditioned</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Guanylate Cyclase - biosynthesis</topic><topic>Guanylate Cyclase - metabolism</topic><topic>Heme - metabolism</topic><topic>Heme Oxygenase (Decyclizing) - analysis</topic><topic>Hemin - pharmacology</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Rats</topic><topic>Sodium Compounds - pharmacology</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHRISTODOULIDES, N</creatorcontrib><creatorcontrib>DURANTE, W</creatorcontrib><creatorcontrib>KROLL, M. H</creatorcontrib><creatorcontrib>SCHAFER, A. I</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHRISTODOULIDES, N</au><au>DURANTE, W</au><au>KROLL, M. H</au><au>SCHAFER, A. I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>1995-05-01</date><risdate>1995</risdate><volume>91</volume><issue>9</issue><spage>2306</spage><epage>2309</epage><pages>2306-2309</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Carbon monoxide (CO), like nitric oxide (NO), stimulates soluble guanylyl cyclase and thereby raises intracellular levels of cGMP. We examined the endogenous capacity of vascular smooth muscle cells (SMCs) to produce CO from heme through the activity of heme oxygenases.
Cultured SMCs from rat aorta (RASMCs) expressed immunoreactive inducible heme oxygenase-1 (HO-1) and constitutive HO-2. Treatment of RASMCs with hemin and sodium arsenite, which are inducers of HO-1, stimulated RASMC cGMP without stimulating nitrite release or inducible NO synthase expression, and the induced elevations of cGMP were not inhibited by the NO synthase inhibitor NG-methyl-L-arginine. Induced CO from RASMCs likewise caused elevation of cGMP levels in platelets coincubated with the vascular cells. Zinc protoporphyrin IX, an inhibitor of HO, reversed the inducible increases in platelet cGMP.
These results indicate that vascular SMCs have both constitutive and inducible HO activity, and they respond to specific stimuli to generate guanylyl cyclase-stimulatory CO in the same SMCs and in coincubated platelets.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>7729015</pmid><doi>10.1161/01.cir.91.9.2306</doi><tpages>4</tpages></addata></record> |
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subjects | Animals Aorta - metabolism Arsenites - pharmacology Biological and medical sciences Blood Platelets - drug effects Blood Platelets - metabolism Blood vessels and receptors Blotting, Western Carbon Monoxide - metabolism Cells, Cultured Culture Media, Conditioned Fundamental and applied biological sciences. Psychology Guanylate Cyclase - biosynthesis Guanylate Cyclase - metabolism Heme - metabolism Heme Oxygenase (Decyclizing) - analysis Hemin - pharmacology Muscle, Smooth, Vascular - metabolism Rats Sodium Compounds - pharmacology Vertebrates: cardiovascular system |
title | Vascular smooth muscle cell heme oxygenases generate guanylyl cyclase-stimulatory carbon monoxide |
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