Relaxant Effect of a Water Soluble Carbon Monoxide-Releasing Molecule (CORM-3) on Spontaneously Hypertensive Rat Aortas
Purpose Both carbon monoxide (CO) and nitric oxide (NO) are two gaseous molecules performing relevant functions in mammals. In order to better understand their actions in the cardiovascular system, we have investigated the effects of CORM-3, (tricarbonylchloro(glycinato)ruthenium(II), a water solubl...
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| Veröffentlicht in: | Cardiovascular drugs and therapy 2012-08, Vol.26 (4), p.285-292 |
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| creator | Failli, Paola Vannacci, Alfredo Di Cesare Mannelli, Lorenzo Motterlini, Roberto Masini, Emanuela |
| description | Purpose
Both carbon monoxide (CO) and nitric oxide (NO) are two gaseous molecules performing relevant functions in mammals. In order to better understand their actions in the cardiovascular system, we have investigated the effects of CORM-3, (tricarbonylchloro(glycinato)ruthenium(II), a water soluble CO-releasing molecule and SNAP (S-nitroso-N-acetyl-DL-penicillamine, a well known NO-releasing molecule) on aortas of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR).
Methods
The isometric contraction of angiotensin II (AT-II) and endothelin-1 (ET-1) was evaluated in endothelium-denuded aortic strips.
Results
In control conditions, AT-II induced a similar concentration-dependent contraction in both WKY and SHR, while ET-1 was more effective in SHR aortic strips. CORM-3 or SNAP (10
−7
–3 × 10
−4
M) reduced the contraction induced by AT-II or ET-1 in a concentration-dependent way. Whereas the median inhibitory concentration of SNAP was significantly lower in WKY than in SHR, CORM-3 had a similar effect in both strains. The scaffold compound
i
CORM-3 was ineffective. Pretreatment with an inhibitor of soluble guanylyl cyclase (ODQ, 3 × 10
−6
M) marginally reduced CORM-3 relaxation in both strains, whereas it reduced relaxation induced by SNAP in WKY and, to a lesser extent, in SHR. The benzylindazole derivative YC-1 (10
−6
M), a sensitizer of soluble guanylate cyclase to the action of NO, significantly increased the relaxant effect of SNAP in AT-II precontracted aortic strips. The blocker of calcium-activated potassium channels, charybdotoxin (10
−8
M), reduced the relaxation induced by CORM-3 in both strains.
Conclusions
Different mechanisms seem to be implicated in CO- and NO-mediated vascular relaxation. Since the relaxant properties of CO are conserved in SHR aortas, CORM-3 could be a new potential agent for the treatment of hypertension, when NO donors show sub-optimal or absent responses. |
| doi_str_mv | 10.1007/s10557-012-6400-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1038617518</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1030348478</sourcerecordid><originalsourceid>FETCH-LOGICAL-c544t-104fba1168cf1370b14cfe84ddfd77cf35f766d332ebfdb7ef661c532dc1917d3</originalsourceid><addsrcrecordid>eNqN0V1rFDEUBuAgil2rP8AbCYjQXqTmOzOXZWltoaWwVbwcMpmTMmU2WZOZ2v33zTLrB4LQq0DynJNzeBF6z-gJo9R8zowqZQhlnGhJKdEv0IIpI4jhkr1EC1pzSgSn-gC9yfmelpq6rl6jA86N1qoSC_RzBYN9tGHEZ96DG3H02OLvdoSEb-MwtQPgpU1tDPg6hvjYd0BKCdjch7tyNYCbCjla3qyuiTjGxd1uYhhtgDjlYYsvthtII4TcPwBe2RGfxjTa_Ba98nbI8G5_HqJv52dflxfk6ubL5fL0ijgl5UgYlb61jOnKeSYMbZl0HirZdb4zxnmhfNmkE4JD67vWgNeaOSV451jNTCcO0dHcd5Pijwny2Kz77GAY5gEbRkWlmVGseg6lQlbS7OjHf-h9nFIoixTF66pWNedFsVm5FHNO4JtN6tc2bQtqdgE2c4BNCbDZBdjoUvNh33lq19D9rviVWAGf9sBmZwefbHB9_uM0pxWTqjg-u1yewh2kv0f83-9PPoCxsA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1029895922</pqid></control><display><type>article</type><title>Relaxant Effect of a Water Soluble Carbon Monoxide-Releasing Molecule (CORM-3) on Spontaneously Hypertensive Rat Aortas</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Failli, Paola ; Vannacci, Alfredo ; Di Cesare Mannelli, Lorenzo ; Motterlini, Roberto ; Masini, Emanuela</creator><creatorcontrib>Failli, Paola ; Vannacci, Alfredo ; Di Cesare Mannelli, Lorenzo ; Motterlini, Roberto ; Masini, Emanuela</creatorcontrib><description>Purpose
Both carbon monoxide (CO) and nitric oxide (NO) are two gaseous molecules performing relevant functions in mammals. In order to better understand their actions in the cardiovascular system, we have investigated the effects of CORM-3, (tricarbonylchloro(glycinato)ruthenium(II), a water soluble CO-releasing molecule and SNAP (S-nitroso-N-acetyl-DL-penicillamine, a well known NO-releasing molecule) on aortas of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR).
Methods
The isometric contraction of angiotensin II (AT-II) and endothelin-1 (ET-1) was evaluated in endothelium-denuded aortic strips.
Results
In control conditions, AT-II induced a similar concentration-dependent contraction in both WKY and SHR, while ET-1 was more effective in SHR aortic strips. CORM-3 or SNAP (10
−7
–3 × 10
−4
M) reduced the contraction induced by AT-II or ET-1 in a concentration-dependent way. Whereas the median inhibitory concentration of SNAP was significantly lower in WKY than in SHR, CORM-3 had a similar effect in both strains. The scaffold compound
i
CORM-3 was ineffective. Pretreatment with an inhibitor of soluble guanylyl cyclase (ODQ, 3 × 10
−6
M) marginally reduced CORM-3 relaxation in both strains, whereas it reduced relaxation induced by SNAP in WKY and, to a lesser extent, in SHR. The benzylindazole derivative YC-1 (10
−6
M), a sensitizer of soluble guanylate cyclase to the action of NO, significantly increased the relaxant effect of SNAP in AT-II precontracted aortic strips. The blocker of calcium-activated potassium channels, charybdotoxin (10
−8
M), reduced the relaxation induced by CORM-3 in both strains.
Conclusions
Different mechanisms seem to be implicated in CO- and NO-mediated vascular relaxation. Since the relaxant properties of CO are conserved in SHR aortas, CORM-3 could be a new potential agent for the treatment of hypertension, when NO donors show sub-optimal or absent responses.</description><identifier>ISSN: 0920-3206</identifier><identifier>EISSN: 1573-7241</identifier><identifier>DOI: 10.1007/s10557-012-6400-6</identifier><identifier>PMID: 22766583</identifier><identifier>CODEN: CDTHET</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Angiotensin II - pharmacology ; Animals ; Aorta - drug effects ; Aorta - metabolism ; Aorta - physiopathology ; Arterial hypertension. Arterial hypotension ; Biological and medical sciences ; Blood and lymphatic vessels ; Carbon monoxide ; Carbon Monoxide - metabolism ; Cardiology ; Cardiology. Vascular system ; Cardiovascular system ; Charybdotoxin - pharmacology ; Drugs ; Endothelin-1 - pharmacology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - physiopathology ; Guanylate Cyclase - metabolism ; Hypertension ; Hypertension - drug therapy ; Hypertension - metabolism ; Hypertension - physiopathology ; Male ; Mammals ; Medical sciences ; Medicine ; Medicine & Public Health ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - metabolism ; Muscle, Smooth, Vascular - physiopathology ; Nitric oxide ; Nitric Oxide - metabolism ; Nitric Oxide Donors - pharmacology ; Organometallic Compounds - pharmacology ; Pharmacology. Drug treatments ; Potassium Channels, Calcium-Activated - metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Receptors, Cytoplasmic and Nuclear - metabolism ; S-Nitroso-N-Acetylpenicillamine - pharmacology ; Soluble Guanylyl Cyclase ; Vasoconstriction - drug effects ; Vasodilation - drug effects ; Vasodilator Agents - pharmacology ; Water - chemistry ; Water wells</subject><ispartof>Cardiovascular drugs and therapy, 2012-08, Vol.26 (4), p.285-292</ispartof><rights>Springer Science+Business Media, LLC 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c544t-104fba1168cf1370b14cfe84ddfd77cf35f766d332ebfdb7ef661c532dc1917d3</citedby><cites>FETCH-LOGICAL-c544t-104fba1168cf1370b14cfe84ddfd77cf35f766d332ebfdb7ef661c532dc1917d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10557-012-6400-6$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10557-012-6400-6$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>315,782,786,27933,27934,41497,42566,51328</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26208145$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22766583$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Failli, Paola</creatorcontrib><creatorcontrib>Vannacci, Alfredo</creatorcontrib><creatorcontrib>Di Cesare Mannelli, Lorenzo</creatorcontrib><creatorcontrib>Motterlini, Roberto</creatorcontrib><creatorcontrib>Masini, Emanuela</creatorcontrib><title>Relaxant Effect of a Water Soluble Carbon Monoxide-Releasing Molecule (CORM-3) on Spontaneously Hypertensive Rat Aortas</title><title>Cardiovascular drugs and therapy</title><addtitle>Cardiovasc Drugs Ther</addtitle><addtitle>Cardiovasc Drugs Ther</addtitle><description>Purpose
Both carbon monoxide (CO) and nitric oxide (NO) are two gaseous molecules performing relevant functions in mammals. In order to better understand their actions in the cardiovascular system, we have investigated the effects of CORM-3, (tricarbonylchloro(glycinato)ruthenium(II), a water soluble CO-releasing molecule and SNAP (S-nitroso-N-acetyl-DL-penicillamine, a well known NO-releasing molecule) on aortas of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR).
Methods
The isometric contraction of angiotensin II (AT-II) and endothelin-1 (ET-1) was evaluated in endothelium-denuded aortic strips.
Results
In control conditions, AT-II induced a similar concentration-dependent contraction in both WKY and SHR, while ET-1 was more effective in SHR aortic strips. CORM-3 or SNAP (10
−7
–3 × 10
−4
M) reduced the contraction induced by AT-II or ET-1 in a concentration-dependent way. Whereas the median inhibitory concentration of SNAP was significantly lower in WKY than in SHR, CORM-3 had a similar effect in both strains. The scaffold compound
i
CORM-3 was ineffective. Pretreatment with an inhibitor of soluble guanylyl cyclase (ODQ, 3 × 10
−6
M) marginally reduced CORM-3 relaxation in both strains, whereas it reduced relaxation induced by SNAP in WKY and, to a lesser extent, in SHR. The benzylindazole derivative YC-1 (10
−6
M), a sensitizer of soluble guanylate cyclase to the action of NO, significantly increased the relaxant effect of SNAP in AT-II precontracted aortic strips. The blocker of calcium-activated potassium channels, charybdotoxin (10
−8
M), reduced the relaxation induced by CORM-3 in both strains.
Conclusions
Different mechanisms seem to be implicated in CO- and NO-mediated vascular relaxation. Since the relaxant properties of CO are conserved in SHR aortas, CORM-3 could be a new potential agent for the treatment of hypertension, when NO donors show sub-optimal or absent responses.</description><subject>Angiotensin II - pharmacology</subject><subject>Animals</subject><subject>Aorta - drug effects</subject><subject>Aorta - metabolism</subject><subject>Aorta - physiopathology</subject><subject>Arterial hypertension. Arterial hypotension</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Carbon monoxide</subject><subject>Carbon Monoxide - metabolism</subject><subject>Cardiology</subject><subject>Cardiology. Vascular system</subject><subject>Cardiovascular system</subject><subject>Charybdotoxin - pharmacology</subject><subject>Drugs</subject><subject>Endothelin-1 - pharmacology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Guanylate Cyclase - metabolism</subject><subject>Hypertension</subject><subject>Hypertension - drug therapy</subject><subject>Hypertension - metabolism</subject><subject>Hypertension - physiopathology</subject><subject>Male</subject><subject>Mammals</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - metabolism</subject><subject>Muscle, Smooth, Vascular - physiopathology</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Organometallic Compounds - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Potassium Channels, Calcium-Activated - metabolism</subject><subject>Rats</subject><subject>Rats, Inbred SHR</subject><subject>Rats, Inbred WKY</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>S-Nitroso-N-Acetylpenicillamine - pharmacology</subject><subject>Soluble Guanylyl Cyclase</subject><subject>Vasoconstriction - drug effects</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilator Agents - pharmacology</subject><subject>Water - chemistry</subject><subject>Water wells</subject><issn>0920-3206</issn><issn>1573-7241</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqN0V1rFDEUBuAgil2rP8AbCYjQXqTmOzOXZWltoaWwVbwcMpmTMmU2WZOZ2v33zTLrB4LQq0DynJNzeBF6z-gJo9R8zowqZQhlnGhJKdEv0IIpI4jhkr1EC1pzSgSn-gC9yfmelpq6rl6jA86N1qoSC_RzBYN9tGHEZ96DG3H02OLvdoSEb-MwtQPgpU1tDPg6hvjYd0BKCdjch7tyNYCbCjla3qyuiTjGxd1uYhhtgDjlYYsvthtII4TcPwBe2RGfxjTa_Ba98nbI8G5_HqJv52dflxfk6ubL5fL0ijgl5UgYlb61jOnKeSYMbZl0HirZdb4zxnmhfNmkE4JD67vWgNeaOSV451jNTCcO0dHcd5Pijwny2Kz77GAY5gEbRkWlmVGseg6lQlbS7OjHf-h9nFIoixTF66pWNedFsVm5FHNO4JtN6tc2bQtqdgE2c4BNCbDZBdjoUvNh33lq19D9rviVWAGf9sBmZwefbHB9_uM0pxWTqjg-u1yewh2kv0f83-9PPoCxsA</recordid><startdate>20120801</startdate><enddate>20120801</enddate><creator>Failli, Paola</creator><creator>Vannacci, Alfredo</creator><creator>Di Cesare Mannelli, Lorenzo</creator><creator>Motterlini, Roberto</creator><creator>Masini, Emanuela</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7Z</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>7U1</scope><scope>7U2</scope><scope>C1K</scope></search><sort><creationdate>20120801</creationdate><title>Relaxant Effect of a Water Soluble Carbon Monoxide-Releasing Molecule (CORM-3) on Spontaneously Hypertensive Rat Aortas</title><author>Failli, Paola ; Vannacci, Alfredo ; Di Cesare Mannelli, Lorenzo ; Motterlini, Roberto ; Masini, Emanuela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c544t-104fba1168cf1370b14cfe84ddfd77cf35f766d332ebfdb7ef661c532dc1917d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Angiotensin II - pharmacology</topic><topic>Animals</topic><topic>Aorta - drug effects</topic><topic>Aorta - metabolism</topic><topic>Aorta - physiopathology</topic><topic>Arterial hypertension. Arterial hypotension</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Carbon monoxide</topic><topic>Carbon Monoxide - metabolism</topic><topic>Cardiology</topic><topic>Cardiology. Vascular system</topic><topic>Cardiovascular system</topic><topic>Charybdotoxin - pharmacology</topic><topic>Drugs</topic><topic>Endothelin-1 - pharmacology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Guanylate Cyclase - metabolism</topic><topic>Hypertension</topic><topic>Hypertension - drug therapy</topic><topic>Hypertension - metabolism</topic><topic>Hypertension - physiopathology</topic><topic>Male</topic><topic>Mammals</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - metabolism</topic><topic>Muscle, Smooth, Vascular - physiopathology</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Organometallic Compounds - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Potassium Channels, Calcium-Activated - metabolism</topic><topic>Rats</topic><topic>Rats, Inbred SHR</topic><topic>Rats, Inbred WKY</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>S-Nitroso-N-Acetylpenicillamine - pharmacology</topic><topic>Soluble Guanylyl Cyclase</topic><topic>Vasoconstriction - drug effects</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilator Agents - pharmacology</topic><topic>Water - chemistry</topic><topic>Water wells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Failli, Paola</creatorcontrib><creatorcontrib>Vannacci, Alfredo</creatorcontrib><creatorcontrib>Di Cesare Mannelli, Lorenzo</creatorcontrib><creatorcontrib>Motterlini, Roberto</creatorcontrib><creatorcontrib>Masini, Emanuela</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 Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Cardiovascular drugs and therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Failli, Paola</au><au>Vannacci, Alfredo</au><au>Di Cesare Mannelli, Lorenzo</au><au>Motterlini, Roberto</au><au>Masini, Emanuela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relaxant Effect of a Water Soluble Carbon Monoxide-Releasing Molecule (CORM-3) on Spontaneously Hypertensive Rat Aortas</atitle><jtitle>Cardiovascular drugs and therapy</jtitle><stitle>Cardiovasc Drugs Ther</stitle><addtitle>Cardiovasc Drugs Ther</addtitle><date>2012-08-01</date><risdate>2012</risdate><volume>26</volume><issue>4</issue><spage>285</spage><epage>292</epage><pages>285-292</pages><issn>0920-3206</issn><eissn>1573-7241</eissn><coden>CDTHET</coden><abstract>Purpose
Both carbon monoxide (CO) and nitric oxide (NO) are two gaseous molecules performing relevant functions in mammals. In order to better understand their actions in the cardiovascular system, we have investigated the effects of CORM-3, (tricarbonylchloro(glycinato)ruthenium(II), a water soluble CO-releasing molecule and SNAP (S-nitroso-N-acetyl-DL-penicillamine, a well known NO-releasing molecule) on aortas of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR).
Methods
The isometric contraction of angiotensin II (AT-II) and endothelin-1 (ET-1) was evaluated in endothelium-denuded aortic strips.
Results
In control conditions, AT-II induced a similar concentration-dependent contraction in both WKY and SHR, while ET-1 was more effective in SHR aortic strips. CORM-3 or SNAP (10
−7
–3 × 10
−4
M) reduced the contraction induced by AT-II or ET-1 in a concentration-dependent way. Whereas the median inhibitory concentration of SNAP was significantly lower in WKY than in SHR, CORM-3 had a similar effect in both strains. The scaffold compound
i
CORM-3 was ineffective. Pretreatment with an inhibitor of soluble guanylyl cyclase (ODQ, 3 × 10
−6
M) marginally reduced CORM-3 relaxation in both strains, whereas it reduced relaxation induced by SNAP in WKY and, to a lesser extent, in SHR. The benzylindazole derivative YC-1 (10
−6
M), a sensitizer of soluble guanylate cyclase to the action of NO, significantly increased the relaxant effect of SNAP in AT-II precontracted aortic strips. The blocker of calcium-activated potassium channels, charybdotoxin (10
−8
M), reduced the relaxation induced by CORM-3 in both strains.
Conclusions
Different mechanisms seem to be implicated in CO- and NO-mediated vascular relaxation. Since the relaxant properties of CO are conserved in SHR aortas, CORM-3 could be a new potential agent for the treatment of hypertension, when NO donors show sub-optimal or absent responses.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>22766583</pmid><doi>10.1007/s10557-012-6400-6</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0920-3206 |
| ispartof | Cardiovascular drugs and therapy, 2012-08, Vol.26 (4), p.285-292 |
| issn | 0920-3206 1573-7241 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1038617518 |
| source | MEDLINE; SpringerNature Journals |
| subjects | Angiotensin II - pharmacology Animals Aorta - drug effects Aorta - metabolism Aorta - physiopathology Arterial hypertension. Arterial hypotension Biological and medical sciences Blood and lymphatic vessels Carbon monoxide Carbon Monoxide - metabolism Cardiology Cardiology. Vascular system Cardiovascular system Charybdotoxin - pharmacology Drugs Endothelin-1 - pharmacology Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Endothelium, Vascular - physiopathology Guanylate Cyclase - metabolism Hypertension Hypertension - drug therapy Hypertension - metabolism Hypertension - physiopathology Male Mammals Medical sciences Medicine Medicine & Public Health Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - physiopathology Nitric oxide Nitric Oxide - metabolism Nitric Oxide Donors - pharmacology Organometallic Compounds - pharmacology Pharmacology. Drug treatments Potassium Channels, Calcium-Activated - metabolism Rats Rats, Inbred SHR Rats, Inbred WKY Receptors, Cytoplasmic and Nuclear - metabolism S-Nitroso-N-Acetylpenicillamine - pharmacology Soluble Guanylyl Cyclase Vasoconstriction - drug effects Vasodilation - drug effects Vasodilator Agents - pharmacology Water - chemistry Water wells |
| title | Relaxant Effect of a Water Soluble Carbon Monoxide-Releasing Molecule (CORM-3) on Spontaneously Hypertensive Rat Aortas |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T11%3A01%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Relaxant%20Effect%20of%20a%20Water%20Soluble%20Carbon%20Monoxide-Releasing%20Molecule%20(CORM-3)%20on%20Spontaneously%20Hypertensive%20Rat%20Aortas&rft.jtitle=Cardiovascular%20drugs%20and%20therapy&rft.au=Failli,%20Paola&rft.date=2012-08-01&rft.volume=26&rft.issue=4&rft.spage=285&rft.epage=292&rft.pages=285-292&rft.issn=0920-3206&rft.eissn=1573-7241&rft.coden=CDTHET&rft_id=info:doi/10.1007/s10557-012-6400-6&rft_dat=%3Cproquest_cross%3E1030348478%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1029895922&rft_id=info:pmid/22766583&rfr_iscdi=true |