Positive and negative inotropic effects of NO donors in atrial and ventricular fibres of the frog heart
The cardiac effects of the NO donors sodium nitroprusside (SNP), S -nitroso- N -acetyl-penicillamine (SNAP) and 3-morpholino-sydnonimine (SIN-1) were studied in frog fibres to evaluate the contribution of cyclic GMP-dependent mechanisms. SNP and SNAP (0·1-100 μM) reduced the force of contraction i...
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| Veröffentlicht in: | The Journal of physiology 1999-07, Vol.518 (2), p.449-461 |
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| creator | Jean-Michel Chesnais Rodolphe Fischmeister Pierre-François Méry |
| description | The cardiac effects of the NO donors sodium nitroprusside (SNP), S -nitroso- N -acetyl-penicillamine (SNAP) and 3-morpholino-sydnonimine (SIN-1) were studied in frog fibres to evaluate the contribution
of cyclic GMP-dependent mechanisms.
SNP and SNAP (0·1-100 μM) reduced the force of contraction in a concentration-dependent manner in atrial and ventricular fibres.
This effect was associated with a reduction in the time to peak ( T TP ) and the time for half-relaxation of contraction ( T ½ ).
SIN-1 (100 μM) also reduced the force of contraction in two-thirds of the atrial fibres. However, it exerted a positive inotropic
effect in the remaining atrial fibres, as well as in most ventricular fibres.
The guanylyl cyclase inhibitor 1 H -[1,2,4]oxidiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 μM) antagonized the negative inotropic effects of SIN-1 (50 μM) and SNAP
(25 μM) but had no effect on the positive inotropic response to SIN-1 (100 μM).
In the presence of SIN-1, superoxide dismutase (SOD, 50-200 U ml â1 ) either potentiated the negative inotropic effect or turned the positive inotropic effect of the drug into a negative effect.
SOD had no effects when applied alone or in the presence of SNAP.
6-Anilino-5,8-quinolinedione (LY 83583, 3-30 μM), a superoxide anion generator also known as a cyclic GMP-lowering agent,
exerted a positive inotropic effect, which was antagonized by SOD (200-370 U ml â1 ) but not by ODQ (10 μM).
We conclude that SNP, SNAP and SIN-1 exert cyclic GMP-dependent negative inotropic effects, which are attributed to the generation
of NO. In addition, SIN-1 and LY 83583 exert cyclic GMP-independent positive inotropic effects, which require the generation
of superoxide anion. |
| doi_str_mv | 10.1111/j.1469-7793.1999.0449p.x |
| format | Article |
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of cyclic GMP-dependent mechanisms.
SNP and SNAP (0·1-100 μM) reduced the force of contraction in a concentration-dependent manner in atrial and ventricular fibres.
This effect was associated with a reduction in the time to peak ( T TP ) and the time for half-relaxation of contraction ( T ½ ).
SIN-1 (100 μM) also reduced the force of contraction in two-thirds of the atrial fibres. However, it exerted a positive inotropic
effect in the remaining atrial fibres, as well as in most ventricular fibres.
The guanylyl cyclase inhibitor 1 H -[1,2,4]oxidiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 μM) antagonized the negative inotropic effects of SIN-1 (50 μM) and SNAP
(25 μM) but had no effect on the positive inotropic response to SIN-1 (100 μM).
In the presence of SIN-1, superoxide dismutase (SOD, 50-200 U ml â1 ) either potentiated the negative inotropic effect or turned the positive inotropic effect of the drug into a negative effect.
SOD had no effects when applied alone or in the presence of SNAP.
6-Anilino-5,8-quinolinedione (LY 83583, 3-30 μM), a superoxide anion generator also known as a cyclic GMP-lowering agent,
exerted a positive inotropic effect, which was antagonized by SOD (200-370 U ml â1 ) but not by ODQ (10 μM).
We conclude that SNP, SNAP and SIN-1 exert cyclic GMP-dependent negative inotropic effects, which are attributed to the generation
of NO. In addition, SIN-1 and LY 83583 exert cyclic GMP-independent positive inotropic effects, which require the generation
of superoxide anion.</description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1111/j.1469-7793.1999.0449p.x</identifier><identifier>PMID: 10381591</identifier><language>eng</language><publisher>Oxford, UK: The Physiological Society</publisher><subject>Aminoquinolines - pharmacology ; Animals ; Cardiology and cardiovascular system ; Cyclic GMP - metabolism ; Enzyme Inhibitors - pharmacology ; Guanylate Cyclase - antagonists & inhibitors ; Half-Life ; Heart - drug effects ; Heart Atria - drug effects ; Heart Ventricles - drug effects ; Human health and pathology ; In Vitro Techniques ; Life Sciences ; Molsidomine - analogs & derivatives ; Molsidomine - pharmacology ; Muscle Fibers, Skeletal - drug effects ; Myocardial Contraction - drug effects ; Nitric Oxide Donors - pharmacology ; Nitroprusside - pharmacology ; Original ; Penicillamine - analogs & derivatives ; Penicillamine - pharmacology ; Pharmaceutical sciences ; Pharmacology ; Rana esculenta ; S-Nitroso-N-Acetylpenicillamine</subject><ispartof>The Journal of physiology, 1999-07, Vol.518 (2), p.449-461</ispartof><rights>1999 The Journal of Physiology © 1999 The Physiological Society</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>The Physiological Society 1999 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5359-20773d63b4328a7c6257f95e49a1a338fce63ba841f1dae9a0c4832256b2514a3</citedby><cites>FETCH-LOGICAL-c5359-20773d63b4328a7c6257f95e49a1a338fce63ba841f1dae9a0c4832256b2514a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2269428/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2269428/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27903,27904,45553,45554,46387,46811,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10381591$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://universite-paris-saclay.hal.science/hal-03612184$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Jean-Michel Chesnais</creatorcontrib><creatorcontrib>Rodolphe Fischmeister</creatorcontrib><creatorcontrib>Pierre-François Méry</creatorcontrib><title>Positive and negative inotropic effects of NO donors in atrial and ventricular fibres of the frog heart</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description>The cardiac effects of the NO donors sodium nitroprusside (SNP), S -nitroso- N -acetyl-penicillamine (SNAP) and 3-morpholino-sydnonimine (SIN-1) were studied in frog fibres to evaluate the contribution
of cyclic GMP-dependent mechanisms.
SNP and SNAP (0·1-100 μM) reduced the force of contraction in a concentration-dependent manner in atrial and ventricular fibres.
This effect was associated with a reduction in the time to peak ( T TP ) and the time for half-relaxation of contraction ( T ½ ).
SIN-1 (100 μM) also reduced the force of contraction in two-thirds of the atrial fibres. However, it exerted a positive inotropic
effect in the remaining atrial fibres, as well as in most ventricular fibres.
The guanylyl cyclase inhibitor 1 H -[1,2,4]oxidiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 μM) antagonized the negative inotropic effects of SIN-1 (50 μM) and SNAP
(25 μM) but had no effect on the positive inotropic response to SIN-1 (100 μM).
In the presence of SIN-1, superoxide dismutase (SOD, 50-200 U ml â1 ) either potentiated the negative inotropic effect or turned the positive inotropic effect of the drug into a negative effect.
SOD had no effects when applied alone or in the presence of SNAP.
6-Anilino-5,8-quinolinedione (LY 83583, 3-30 μM), a superoxide anion generator also known as a cyclic GMP-lowering agent,
exerted a positive inotropic effect, which was antagonized by SOD (200-370 U ml â1 ) but not by ODQ (10 μM).
We conclude that SNP, SNAP and SIN-1 exert cyclic GMP-dependent negative inotropic effects, which are attributed to the generation
of NO. In addition, SIN-1 and LY 83583 exert cyclic GMP-independent positive inotropic effects, which require the generation
of superoxide anion.</description><subject>Aminoquinolines - pharmacology</subject><subject>Animals</subject><subject>Cardiology and cardiovascular system</subject><subject>Cyclic GMP - metabolism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Guanylate Cyclase - antagonists & inhibitors</subject><subject>Half-Life</subject><subject>Heart - drug effects</subject><subject>Heart Atria - drug effects</subject><subject>Heart Ventricles - drug effects</subject><subject>Human health and pathology</subject><subject>In Vitro Techniques</subject><subject>Life Sciences</subject><subject>Molsidomine - analogs & derivatives</subject><subject>Molsidomine - pharmacology</subject><subject>Muscle Fibers, Skeletal - drug effects</subject><subject>Myocardial Contraction - drug effects</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitroprusside - pharmacology</subject><subject>Original</subject><subject>Penicillamine - analogs & derivatives</subject><subject>Penicillamine - pharmacology</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacology</subject><subject>Rana esculenta</subject><subject>S-Nitroso-N-Acetylpenicillamine</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkV9v0zAUxS0EYt3gKyA_gXhI8N_ElhDSNMEGqtgexrPlOnbiKo2LnXbrt8dpqmnwhF_s6_s7x746AECMSpzXp3WJWSWLupa0xFLKEjEmt-XjC7B4arwEC4QIKWjN8Rk4T2mNEKZIytfgDCMqMJd4Adq7kPzo9xbqoYGDbfWx8EMYY9h6A61z1owJBgd_3sImDCGm3IZ6jF73R9XeDrkwu15H6Pwq2iM9dha6GFrYWR3HN-CV032yb0_7Bfj17ev91U2xvL3-fnW5LAynXBYE1TVtKrpilAhdm4rw2klumdRYUyqcsbmpBcMON9pKjQwTlBBerQjHTNML8GX23e5WG9uY6Wu6V9voNzoeVNBe_d0ZfKfasFeEVJIRkQ0-zgbdP7Kby6Wa7hCtMMGC7XFm358ei-H3zqZRbXwytu_1YMMuqUoKjuuKZFDMoIkhpWjdkzNGakpUrdUUnJqCU1Oi6pioeszSd88HeiacI8zA5xl48L09_Lexuv9xl09Z_uE0r2-7Bx-t2naH5EMKxtvxoDgWiqiJ_ANf5L6s</recordid><startdate>19990715</startdate><enddate>19990715</enddate><creator>Jean-Michel Chesnais</creator><creator>Rodolphe Fischmeister</creator><creator>Pierre-François Méry</creator><general>The Physiological Society</general><general>Blackwell Science Ltd</general><general>Wiley</general><general>Blackwell Science Inc</general><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><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope></search><sort><creationdate>19990715</creationdate><title>Positive and negative inotropic effects of NO donors in atrial and ventricular fibres of the frog heart</title><author>Jean-Michel Chesnais ; Rodolphe Fischmeister ; Pierre-François Méry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5359-20773d63b4328a7c6257f95e49a1a338fce63ba841f1dae9a0c4832256b2514a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Aminoquinolines - pharmacology</topic><topic>Animals</topic><topic>Cardiology and cardiovascular system</topic><topic>Cyclic GMP - metabolism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Guanylate Cyclase - antagonists & inhibitors</topic><topic>Half-Life</topic><topic>Heart - drug effects</topic><topic>Heart Atria - drug effects</topic><topic>Heart Ventricles - drug effects</topic><topic>Human health and pathology</topic><topic>In Vitro Techniques</topic><topic>Life Sciences</topic><topic>Molsidomine - analogs & derivatives</topic><topic>Molsidomine - pharmacology</topic><topic>Muscle Fibers, Skeletal - drug effects</topic><topic>Myocardial Contraction - drug effects</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitroprusside - pharmacology</topic><topic>Original</topic><topic>Penicillamine - analogs & derivatives</topic><topic>Penicillamine - pharmacology</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacology</topic><topic>Rana esculenta</topic><topic>S-Nitroso-N-Acetylpenicillamine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jean-Michel Chesnais</creatorcontrib><creatorcontrib>Rodolphe Fischmeister</creatorcontrib><creatorcontrib>Pierre-François Méry</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><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jean-Michel Chesnais</au><au>Rodolphe Fischmeister</au><au>Pierre-François Méry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Positive and negative inotropic effects of NO donors in atrial and ventricular fibres of the frog heart</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>1999-07-15</date><risdate>1999</risdate><volume>518</volume><issue>2</issue><spage>449</spage><epage>461</epage><pages>449-461</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><abstract>The cardiac effects of the NO donors sodium nitroprusside (SNP), S -nitroso- N -acetyl-penicillamine (SNAP) and 3-morpholino-sydnonimine (SIN-1) were studied in frog fibres to evaluate the contribution
of cyclic GMP-dependent mechanisms.
SNP and SNAP (0·1-100 μM) reduced the force of contraction in a concentration-dependent manner in atrial and ventricular fibres.
This effect was associated with a reduction in the time to peak ( T TP ) and the time for half-relaxation of contraction ( T ½ ).
SIN-1 (100 μM) also reduced the force of contraction in two-thirds of the atrial fibres. However, it exerted a positive inotropic
effect in the remaining atrial fibres, as well as in most ventricular fibres.
The guanylyl cyclase inhibitor 1 H -[1,2,4]oxidiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 μM) antagonized the negative inotropic effects of SIN-1 (50 μM) and SNAP
(25 μM) but had no effect on the positive inotropic response to SIN-1 (100 μM).
In the presence of SIN-1, superoxide dismutase (SOD, 50-200 U ml â1 ) either potentiated the negative inotropic effect or turned the positive inotropic effect of the drug into a negative effect.
SOD had no effects when applied alone or in the presence of SNAP.
6-Anilino-5,8-quinolinedione (LY 83583, 3-30 μM), a superoxide anion generator also known as a cyclic GMP-lowering agent,
exerted a positive inotropic effect, which was antagonized by SOD (200-370 U ml â1 ) but not by ODQ (10 μM).
We conclude that SNP, SNAP and SIN-1 exert cyclic GMP-dependent negative inotropic effects, which are attributed to the generation
of NO. In addition, SIN-1 and LY 83583 exert cyclic GMP-independent positive inotropic effects, which require the generation
of superoxide anion.</abstract><cop>Oxford, UK</cop><pub>The Physiological Society</pub><pmid>10381591</pmid><doi>10.1111/j.1469-7793.1999.0449p.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Free Content; MEDLINE; IngentaConnect Free/Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Aminoquinolines - pharmacology Animals Cardiology and cardiovascular system Cyclic GMP - metabolism Enzyme Inhibitors - pharmacology Guanylate Cyclase - antagonists & inhibitors Half-Life Heart - drug effects Heart Atria - drug effects Heart Ventricles - drug effects Human health and pathology In Vitro Techniques Life Sciences Molsidomine - analogs & derivatives Molsidomine - pharmacology Muscle Fibers, Skeletal - drug effects Myocardial Contraction - drug effects Nitric Oxide Donors - pharmacology Nitroprusside - pharmacology Original Penicillamine - analogs & derivatives Penicillamine - pharmacology Pharmaceutical sciences Pharmacology Rana esculenta S-Nitroso-N-Acetylpenicillamine |
| title | Positive and negative inotropic effects of NO donors in atrial and ventricular fibres of the frog heart |
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