Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca2+ and NO
Departments of Physiology and Internal Medicine, Wayne State University School of Medicine, and John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan 48201 Normally, insulin-like growth factor I (IGF-I) exerts positive effects on cardiac growth and myocardial contractility, but resistan...
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| Veröffentlicht in: | American journal of physiology. Heart and circulatory physiology 1998-09, Vol.275 (3), p.H823-H830 |
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| container_title | American journal of physiology. Heart and circulatory physiology |
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| creator | Ren, Jun Walsh, Mary F Hamaty, Marwan Sowers, James R Brown, Ricardo A |
| description | Departments of Physiology and Internal Medicine, Wayne State
University School of Medicine, and John D. Dingell Veterans Affairs
Medical Center, Detroit, Michigan 48201
Normally,
insulin-like growth factor I (IGF-I) exerts positive effects on cardiac
growth and myocardial contractility, but resistance to its action has
been reported in diabetes. This study was designed to determine whether
IGF-I-induced myocardial contractile action is altered in diabetes as a
result of an intrinsic alteration of contractile properties at
the cellular level. Contractile responses to IGF-I were examined in
left ventricular papillary muscles and ventricular myocytes from normal
and short-term (5-7 days) streptozotocin-induced diabetic rats.
Mechanical properties of muscles and myocytes were evaluated using a
force transducer and an edge detector, respectively. Preparations were
electrically stimulated at 0.5 Hz, and contractile properties analyzed
include peak tension development (PTD) or peak twitch amplitude (PTA),
time to peak contraction/shortening, and time to 90%
relaxation/relengthening. Intracellular
Ca 2+ transients were measured as
fura 2 fluorescence intensity changes. IGF-I (1-500 ng/ml) caused
a dose-dependent increase in PTD and PTA in preparations from normal
but not diabetic animals. IGF-I did not alter time to peak
contraction/shortening or time to 90% relaxation/relengthening.
Pretreatment with the NO synthase inhibitor N -nitro- L -arginine methyl ester
(100 µM) attenuated IGF-I-induced increases in PTD in normal
myocardium but unmasked a positive inotropic action in diabetic
animals. Pretreatment with
N -nitro- L -arginine methyl ester
blocked IGF-I-induced increases in PTA in single myocytes. Consistent
with its inotropic actions on muscles and myocytes, IGF-I induced a
dose-dependent increase in Ca 2+
transients in normal but not diabetic myocytes. These results suggest
that the IGF-I-induced inotropic response is depressed in diabetes
because of an intrinsic alteration at the myocyte level.
Mechanisms underlying this alteration in IGF-I-induced myocardial
response may be related to changes in intracellular Ca 2+ and/or NO production
in diabetes.
insulin-like growth factor I; nitric oxide; papillary muscle; ventricular myocyte; calcium transient |
| doi_str_mv | 10.1152/ajpheart.1998.275.3.H823 |
| format | Article |
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University School of Medicine, and John D. Dingell Veterans Affairs
Medical Center, Detroit, Michigan 48201
Normally,
insulin-like growth factor I (IGF-I) exerts positive effects on cardiac
growth and myocardial contractility, but resistance to its action has
been reported in diabetes. This study was designed to determine whether
IGF-I-induced myocardial contractile action is altered in diabetes as a
result of an intrinsic alteration of contractile properties at
the cellular level. Contractile responses to IGF-I were examined in
left ventricular papillary muscles and ventricular myocytes from normal
and short-term (5-7 days) streptozotocin-induced diabetic rats.
Mechanical properties of muscles and myocytes were evaluated using a
force transducer and an edge detector, respectively. Preparations were
electrically stimulated at 0.5 Hz, and contractile properties analyzed
include peak tension development (PTD) or peak twitch amplitude (PTA),
time to peak contraction/shortening, and time to 90%
relaxation/relengthening. Intracellular
Ca 2+ transients were measured as
fura 2 fluorescence intensity changes. IGF-I (1-500 ng/ml) caused
a dose-dependent increase in PTD and PTA in preparations from normal
but not diabetic animals. IGF-I did not alter time to peak
contraction/shortening or time to 90% relaxation/relengthening.
Pretreatment with the NO synthase inhibitor N -nitro- L -arginine methyl ester
(100 µM) attenuated IGF-I-induced increases in PTD in normal
myocardium but unmasked a positive inotropic action in diabetic
animals. Pretreatment with
N -nitro- L -arginine methyl ester
blocked IGF-I-induced increases in PTA in single myocytes. Consistent
with its inotropic actions on muscles and myocytes, IGF-I induced a
dose-dependent increase in Ca 2+
transients in normal but not diabetic myocytes. These results suggest
that the IGF-I-induced inotropic response is depressed in diabetes
because of an intrinsic alteration at the myocyte level.
Mechanisms underlying this alteration in IGF-I-induced myocardial
response may be related to changes in intracellular Ca 2+ and/or NO production
in diabetes.
insulin-like growth factor I; nitric oxide; papillary muscle; ventricular myocyte; calcium transient</description><identifier>ISSN: 0363-6135</identifier><identifier>ISSN: 0002-9513</identifier><identifier>EISSN: 1522-1539</identifier><identifier>DOI: 10.1152/ajpheart.1998.275.3.H823</identifier><identifier>PMID: 9724285</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Biomechanical Phenomena ; Calcium - metabolism ; Diabetes Mellitus, Experimental - physiopathology ; Electric Stimulation ; Enzyme Inhibitors - pharmacology ; Insulin-Like Growth Factor I - pharmacology ; Male ; Myocardial Contraction - drug effects ; NG-Nitroarginine Methyl Ester - pharmacology ; Nitric Oxide Synthase - antagonists & inhibitors ; Norepinephrine - pharmacology ; Papillary Muscles - physiopathology ; Potassium Chloride - pharmacology ; Rats ; Rats, Sprague-Dawley ; Stimulation, Chemical</subject><ispartof>American journal of physiology. Heart and circulatory physiology, 1998-09, Vol.275 (3), p.H823-H830</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9724285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ren, Jun</creatorcontrib><creatorcontrib>Walsh, Mary F</creatorcontrib><creatorcontrib>Hamaty, Marwan</creatorcontrib><creatorcontrib>Sowers, James R</creatorcontrib><creatorcontrib>Brown, Ricardo A</creatorcontrib><title>Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca2+ and NO</title><title>American journal of physiology. Heart and circulatory physiology</title><addtitle>Am J Physiol</addtitle><description>Departments of Physiology and Internal Medicine, Wayne State
University School of Medicine, and John D. Dingell Veterans Affairs
Medical Center, Detroit, Michigan 48201
Normally,
insulin-like growth factor I (IGF-I) exerts positive effects on cardiac
growth and myocardial contractility, but resistance to its action has
been reported in diabetes. This study was designed to determine whether
IGF-I-induced myocardial contractile action is altered in diabetes as a
result of an intrinsic alteration of contractile properties at
the cellular level. Contractile responses to IGF-I were examined in
left ventricular papillary muscles and ventricular myocytes from normal
and short-term (5-7 days) streptozotocin-induced diabetic rats.
Mechanical properties of muscles and myocytes were evaluated using a
force transducer and an edge detector, respectively. Preparations were
electrically stimulated at 0.5 Hz, and contractile properties analyzed
include peak tension development (PTD) or peak twitch amplitude (PTA),
time to peak contraction/shortening, and time to 90%
relaxation/relengthening. Intracellular
Ca 2+ transients were measured as
fura 2 fluorescence intensity changes. IGF-I (1-500 ng/ml) caused
a dose-dependent increase in PTD and PTA in preparations from normal
but not diabetic animals. IGF-I did not alter time to peak
contraction/shortening or time to 90% relaxation/relengthening.
Pretreatment with the NO synthase inhibitor N -nitro- L -arginine methyl ester
(100 µM) attenuated IGF-I-induced increases in PTD in normal
myocardium but unmasked a positive inotropic action in diabetic
animals. Pretreatment with
N -nitro- L -arginine methyl ester
blocked IGF-I-induced increases in PTA in single myocytes. Consistent
with its inotropic actions on muscles and myocytes, IGF-I induced a
dose-dependent increase in Ca 2+
transients in normal but not diabetic myocytes. These results suggest
that the IGF-I-induced inotropic response is depressed in diabetes
because of an intrinsic alteration at the myocyte level.
Mechanisms underlying this alteration in IGF-I-induced myocardial
response may be related to changes in intracellular Ca 2+ and/or NO production
in diabetes.
insulin-like growth factor I; nitric oxide; papillary muscle; ventricular myocyte; calcium transient</description><subject>Animals</subject><subject>Biomechanical Phenomena</subject><subject>Calcium - metabolism</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>Electric Stimulation</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Insulin-Like Growth Factor I - pharmacology</subject><subject>Male</subject><subject>Myocardial Contraction - drug effects</subject><subject>NG-Nitroarginine Methyl Ester - pharmacology</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Norepinephrine - pharmacology</subject><subject>Papillary Muscles - physiopathology</subject><subject>Potassium Chloride - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Stimulation, Chemical</subject><issn>0363-6135</issn><issn>0002-9513</issn><issn>1522-1539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtOwzAQRS0EgvL4BCSv2KCE2I7zYIcqWioh2MDasuMxCXLjYDuC_j0pFFixGs2ce2dGFyFMspQQTq_k69CC9DEldV2ltOQpS-8qyvbQbMI0IZzV-2iWsYIlBWH8CB2H8JplGS8LdogO65LmtOIzJG9sBA8ad72L3g1dgz2EwfUBcHR4tVwkq4lh3UkFcUtlxF-nr6exsSP0DWBnpiZ62YC1o5UezyW9xLLX-OHxFB0YaQOc7eoJel7cPs3vkvvH5Wp-c5-0tKxiYkihtQLO8iZvCKlLpWtpKJegSK4lz6U2VdYoo6guFCmgVnlVg8nAbDWMnaCL772Dd28jhCjWXdg-JHtwYxAlq0pGST4Jz3fCUa1Bi8F3a-k3YpfJxNNv3nYv7XvnQQztJnTOupeN-AleTJkLJraZT4br_w2L0don-Ii_zj-jGLRhn4GqjY4</recordid><startdate>19980901</startdate><enddate>19980901</enddate><creator>Ren, Jun</creator><creator>Walsh, Mary F</creator><creator>Hamaty, Marwan</creator><creator>Sowers, James R</creator><creator>Brown, Ricardo A</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19980901</creationdate><title>Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca2+ and NO</title><author>Ren, Jun ; Walsh, Mary F ; Hamaty, Marwan ; Sowers, James R ; Brown, Ricardo A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h278t-f16ddbe534c4c1197bd9af25aeb14da54adf80cbfb2d6b16e9b489ef0ef5aeb33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Animals</topic><topic>Biomechanical Phenomena</topic><topic>Calcium - metabolism</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Electric Stimulation</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Insulin-Like Growth Factor I - pharmacology</topic><topic>Male</topic><topic>Myocardial Contraction - drug effects</topic><topic>NG-Nitroarginine Methyl Ester - pharmacology</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Norepinephrine - pharmacology</topic><topic>Papillary Muscles - physiopathology</topic><topic>Potassium Chloride - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Stimulation, Chemical</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ren, Jun</creatorcontrib><creatorcontrib>Walsh, Mary F</creatorcontrib><creatorcontrib>Hamaty, Marwan</creatorcontrib><creatorcontrib>Sowers, James R</creatorcontrib><creatorcontrib>Brown, Ricardo A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</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>Ren, Jun</au><au>Walsh, Mary F</au><au>Hamaty, Marwan</au><au>Sowers, James R</au><au>Brown, Ricardo A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca2+ and NO</atitle><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle><addtitle>Am J Physiol</addtitle><date>1998-09-01</date><risdate>1998</risdate><volume>275</volume><issue>3</issue><spage>H823</spage><epage>H830</epage><pages>H823-H830</pages><issn>0363-6135</issn><issn>0002-9513</issn><eissn>1522-1539</eissn><abstract>Departments of Physiology and Internal Medicine, Wayne State
University School of Medicine, and John D. Dingell Veterans Affairs
Medical Center, Detroit, Michigan 48201
Normally,
insulin-like growth factor I (IGF-I) exerts positive effects on cardiac
growth and myocardial contractility, but resistance to its action has
been reported in diabetes. This study was designed to determine whether
IGF-I-induced myocardial contractile action is altered in diabetes as a
result of an intrinsic alteration of contractile properties at
the cellular level. Contractile responses to IGF-I were examined in
left ventricular papillary muscles and ventricular myocytes from normal
and short-term (5-7 days) streptozotocin-induced diabetic rats.
Mechanical properties of muscles and myocytes were evaluated using a
force transducer and an edge detector, respectively. Preparations were
electrically stimulated at 0.5 Hz, and contractile properties analyzed
include peak tension development (PTD) or peak twitch amplitude (PTA),
time to peak contraction/shortening, and time to 90%
relaxation/relengthening. Intracellular
Ca 2+ transients were measured as
fura 2 fluorescence intensity changes. IGF-I (1-500 ng/ml) caused
a dose-dependent increase in PTD and PTA in preparations from normal
but not diabetic animals. IGF-I did not alter time to peak
contraction/shortening or time to 90% relaxation/relengthening.
Pretreatment with the NO synthase inhibitor N -nitro- L -arginine methyl ester
(100 µM) attenuated IGF-I-induced increases in PTD in normal
myocardium but unmasked a positive inotropic action in diabetic
animals. Pretreatment with
N -nitro- L -arginine methyl ester
blocked IGF-I-induced increases in PTA in single myocytes. Consistent
with its inotropic actions on muscles and myocytes, IGF-I induced a
dose-dependent increase in Ca 2+
transients in normal but not diabetic myocytes. These results suggest
that the IGF-I-induced inotropic response is depressed in diabetes
because of an intrinsic alteration at the myocyte level.
Mechanisms underlying this alteration in IGF-I-induced myocardial
response may be related to changes in intracellular Ca 2+ and/or NO production
in diabetes.
insulin-like growth factor I; nitric oxide; papillary muscle; ventricular myocyte; calcium transient</abstract><cop>United States</cop><pmid>9724285</pmid><doi>10.1152/ajpheart.1998.275.3.H823</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0363-6135 |
| ispartof | American journal of physiology. Heart and circulatory physiology, 1998-09, Vol.275 (3), p.H823-H830 |
| issn | 0363-6135 0002-9513 1522-1539 |
| language | eng |
| recordid | cdi_highwire_physiology_ajpheart_275_3_H823 |
| source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Biomechanical Phenomena Calcium - metabolism Diabetes Mellitus, Experimental - physiopathology Electric Stimulation Enzyme Inhibitors - pharmacology Insulin-Like Growth Factor I - pharmacology Male Myocardial Contraction - drug effects NG-Nitroarginine Methyl Ester - pharmacology Nitric Oxide Synthase - antagonists & inhibitors Norepinephrine - pharmacology Papillary Muscles - physiopathology Potassium Chloride - pharmacology Rats Rats, Sprague-Dawley Stimulation, Chemical |
| title | Altered inotropic response to IGF-I in diabetic rat heart: influence of intracellular Ca2+ and NO |
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