Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings
Departments of Physiology and Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-0622 Insulin attenuates vascular contraction via inhibition of voltage-operated Ca 2+ channels and by enhancement of endothelium-dependent vasodilation. Thus it has been suggested that hypertension-ass...
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| Veröffentlicht in: | American journal of physiology: endocrinology and metabolism 1998-11, Vol.275 (5), p.E882-E887 |
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| creator | Goud, Chetan Pitt, Bertram Webb, R. Clinton Richey, Joyce M |
| description | Departments of Physiology and Internal Medicine, University of
Michigan, Ann Arbor, Michigan 48109-0622
Insulin attenuates vascular contraction via inhibition of
voltage-operated Ca 2+ channels and
by enhancement of endothelium-dependent vasodilation. Thus it has been
suggested that hypertension-associated insulin resistance results from
an insensitivity to the hormone's effects on vascular reactivity. This
hypothesis has been strengthened by reports that thiazolidinediones, a
class of insulin-sensitizing agents, lower blood pressure and improve
insulin responsiveness in hypertensive, insulin-resistant animal
models. We tested the hypothesis that troglitazone enhances the
vasodilating effect of insulin via inhibition of voltage-operated
Ca 2+ channels in vascular smooth
muscle cells. Rat thoracic aortic rings (no endothelium) were suspended
in tissue baths for isometric force measurement. Rings were incubated
with 0.1 DMSO vehicle (control), troglitazone
(10 5 M), insulin
(10 7 U/l), or both
troglitazone and insulin (1 h) and then contracted with phenylephrine
(PE), KCl, or BAY K 8644. Troglitazone increased the
EC 50 values for PE and KCl.
Contractions to BAY K 8644 in troglitazone-treated rings were virtually
abolished. Insulin alone had no effect on contraction. However, when
insulin was combined with troglitazone, the
EC 50 values for PE and KCl were
further increased. Additionally, the maximum contractions
to both PE (14 ± 4% of control) and KCl (12 ± 2% of control)
were reduced. Measurement of Ca 2+
concentration ([Ca 2+ ])
with fura 2-AM in dispersed vascular smooth muscle cells indicated that
neither insulin nor troglitazone alone altered PE-induced increases in
intracellular [Ca 2+ ].
However, troglitazone and insulin together caused a significant reduction in PE-induced increases in intracellular
[Ca 2+ ] (expressed as
percentage of preincubation stimulation to PE: 47 ± 10%, treated;
102 ± 13%, vehicle). These results demonstrate that troglitazone
inhibits Ca 2+ influx and that it
acts synergistically with insulin to attenuate further vascular
contraction via inhibition of voltage-operated Ca 2+ channels.
vascular smooth muscle; calcium channels |
| doi_str_mv | 10.1152/ajpendo.1998.275.5.e882 |
| format | Article |
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Michigan, Ann Arbor, Michigan 48109-0622
Insulin attenuates vascular contraction via inhibition of
voltage-operated Ca 2+ channels and
by enhancement of endothelium-dependent vasodilation. Thus it has been
suggested that hypertension-associated insulin resistance results from
an insensitivity to the hormone's effects on vascular reactivity. This
hypothesis has been strengthened by reports that thiazolidinediones, a
class of insulin-sensitizing agents, lower blood pressure and improve
insulin responsiveness in hypertensive, insulin-resistant animal
models. We tested the hypothesis that troglitazone enhances the
vasodilating effect of insulin via inhibition of voltage-operated
Ca 2+ channels in vascular smooth
muscle cells. Rat thoracic aortic rings (no endothelium) were suspended
in tissue baths for isometric force measurement. Rings were incubated
with 0.1 DMSO vehicle (control), troglitazone
(10 5 M), insulin
(10 7 U/l), or both
troglitazone and insulin (1 h) and then contracted with phenylephrine
(PE), KCl, or BAY K 8644. Troglitazone increased the
EC 50 values for PE and KCl.
Contractions to BAY K 8644 in troglitazone-treated rings were virtually
abolished. Insulin alone had no effect on contraction. However, when
insulin was combined with troglitazone, the
EC 50 values for PE and KCl were
further increased. Additionally, the maximum contractions
to both PE (14 ± 4% of control) and KCl (12 ± 2% of control)
were reduced. Measurement of Ca 2+
concentration ([Ca 2+ ])
with fura 2-AM in dispersed vascular smooth muscle cells indicated that
neither insulin nor troglitazone alone altered PE-induced increases in
intracellular [Ca 2+ ].
However, troglitazone and insulin together caused a significant reduction in PE-induced increases in intracellular
[Ca 2+ ] (expressed as
percentage of preincubation stimulation to PE: 47 ± 10%, treated;
102 ± 13%, vehicle). These results demonstrate that troglitazone
inhibits Ca 2+ influx and that it
acts synergistically with insulin to attenuate further vascular
contraction via inhibition of voltage-operated Ca 2+ channels.
vascular smooth muscle; calcium channels</description><identifier>ISSN: 0193-1849</identifier><identifier>ISSN: 0002-9513</identifier><identifier>EISSN: 1522-1555</identifier><identifier>DOI: 10.1152/ajpendo.1998.275.5.e882</identifier><identifier>PMID: 9815009</identifier><language>eng</language><publisher>United States</publisher><subject>3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology ; Animals ; Aorta, Thoracic - drug effects ; Aorta, Thoracic - physiology ; Calcium - metabolism ; Chromans - pharmacology ; Endothelium, Vascular ; Hypoglycemic Agents - pharmacology ; In Vitro Techniques ; Insulin - pharmacology ; Isometric Contraction - drug effects ; Isometric Contraction - physiology ; Male ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - physiology ; Phenylephrine - pharmacology ; Potassium Chloride - pharmacology ; Rats ; Rats, Sprague-Dawley ; Thiazoles - pharmacology ; Thiazolidinediones ; Troglitazone ; Vasodilator Agents - pharmacology</subject><ispartof>American journal of physiology: endocrinology and metabolism, 1998-11, Vol.275 (5), p.E882-E887</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-1d4ccd588a54894463404e8b5bb9fda648ca30733edf6752bb38c4e6c1b4a5743</citedby><cites>FETCH-LOGICAL-c396t-1d4ccd588a54894463404e8b5bb9fda648ca30733edf6752bb38c4e6c1b4a5743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9815009$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goud, Chetan</creatorcontrib><creatorcontrib>Pitt, Bertram</creatorcontrib><creatorcontrib>Webb, R. Clinton</creatorcontrib><creatorcontrib>Richey, Joyce M</creatorcontrib><title>Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings</title><title>American journal of physiology: endocrinology and metabolism</title><addtitle>Am J Physiol</addtitle><description>Departments of Physiology and Internal Medicine, University of
Michigan, Ann Arbor, Michigan 48109-0622
Insulin attenuates vascular contraction via inhibition of
voltage-operated Ca 2+ channels and
by enhancement of endothelium-dependent vasodilation. Thus it has been
suggested that hypertension-associated insulin resistance results from
an insensitivity to the hormone's effects on vascular reactivity. This
hypothesis has been strengthened by reports that thiazolidinediones, a
class of insulin-sensitizing agents, lower blood pressure and improve
insulin responsiveness in hypertensive, insulin-resistant animal
models. We tested the hypothesis that troglitazone enhances the
vasodilating effect of insulin via inhibition of voltage-operated
Ca 2+ channels in vascular smooth
muscle cells. Rat thoracic aortic rings (no endothelium) were suspended
in tissue baths for isometric force measurement. Rings were incubated
with 0.1 DMSO vehicle (control), troglitazone
(10 5 M), insulin
(10 7 U/l), or both
troglitazone and insulin (1 h) and then contracted with phenylephrine
(PE), KCl, or BAY K 8644. Troglitazone increased the
EC 50 values for PE and KCl.
Contractions to BAY K 8644 in troglitazone-treated rings were virtually
abolished. Insulin alone had no effect on contraction. However, when
insulin was combined with troglitazone, the
EC 50 values for PE and KCl were
further increased. Additionally, the maximum contractions
to both PE (14 ± 4% of control) and KCl (12 ± 2% of control)
were reduced. Measurement of Ca 2+
concentration ([Ca 2+ ])
with fura 2-AM in dispersed vascular smooth muscle cells indicated that
neither insulin nor troglitazone alone altered PE-induced increases in
intracellular [Ca 2+ ].
However, troglitazone and insulin together caused a significant reduction in PE-induced increases in intracellular
[Ca 2+ ] (expressed as
percentage of preincubation stimulation to PE: 47 ± 10%, treated;
102 ± 13%, vehicle). These results demonstrate that troglitazone
inhibits Ca 2+ influx and that it
acts synergistically with insulin to attenuate further vascular
contraction via inhibition of voltage-operated Ca 2+ channels.
vascular smooth muscle; calcium channels</description><subject>3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology</subject><subject>Animals</subject><subject>Aorta, Thoracic - drug effects</subject><subject>Aorta, Thoracic - physiology</subject><subject>Calcium - metabolism</subject><subject>Chromans - pharmacology</subject><subject>Endothelium, Vascular</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Insulin - pharmacology</subject><subject>Isometric Contraction - drug effects</subject><subject>Isometric Contraction - physiology</subject><subject>Male</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - physiology</subject><subject>Phenylephrine - pharmacology</subject><subject>Potassium Chloride - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Thiazoles - pharmacology</subject><subject>Thiazolidinediones</subject><subject>Troglitazone</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0193-1849</issn><issn>0002-9513</issn><issn>1522-1555</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kF9v1SAYxonRzLPpRzBy5V0rtNDCpVk2NVnihfOaUKAtCwcq0Gj36aU5Z84br0je5w9PfgC8x6jGmDYf5cNivA415pzVTU9rWhvGmhfgUNSmwpTSl-CAMG8rzAh_DS5TekAI9ZQ0F-CCM0wR4gcwf9-8iZNN2SooVbbBJxhGaH1anfVQeg1zDJOzWT4Gb2DwUAWf4-4tx6044b4kz8bZ9Vhp41dtNIwyQxniXhutn9Ib8GqULpm35_cK_Li9ub_-Ut19-_z1-tNdpVre5QpropSmjElKGCekawkihg10GPioZUeYki3q29bosetpMwwtU8R0Cg9E0p60V-DDqXeJ4edqUhZHm5RxTnoT1iR6hLoGkaYY-5NRxZBSNKNYoj3KuAmMxM5YnBmLnbEojAUVN4VxSb47f7EOR6P_5s5Qi85P-myn-ZeNRizzlmxwYdrE7ercvfmdn9qfe8Wix5Kt_p99GvTPlj-u8aIx</recordid><startdate>19981101</startdate><enddate>19981101</enddate><creator>Goud, Chetan</creator><creator>Pitt, Bertram</creator><creator>Webb, R. Clinton</creator><creator>Richey, Joyce 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>19981101</creationdate><title>Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings</title><author>Goud, Chetan ; Pitt, Bertram ; Webb, R. Clinton ; Richey, Joyce M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-1d4ccd588a54894463404e8b5bb9fda648ca30733edf6752bb38c4e6c1b4a5743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology</topic><topic>Animals</topic><topic>Aorta, Thoracic - drug effects</topic><topic>Aorta, Thoracic - physiology</topic><topic>Calcium - metabolism</topic><topic>Chromans - pharmacology</topic><topic>Endothelium, Vascular</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Insulin - pharmacology</topic><topic>Isometric Contraction - drug effects</topic><topic>Isometric Contraction - physiology</topic><topic>Male</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - physiology</topic><topic>Phenylephrine - pharmacology</topic><topic>Potassium Chloride - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Thiazoles - pharmacology</topic><topic>Thiazolidinediones</topic><topic>Troglitazone</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Goud, Chetan</creatorcontrib><creatorcontrib>Pitt, Bertram</creatorcontrib><creatorcontrib>Webb, R. Clinton</creatorcontrib><creatorcontrib>Richey, Joyce 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: endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Goud, Chetan</au><au>Pitt, Bertram</au><au>Webb, R. Clinton</au><au>Richey, Joyce M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings</atitle><jtitle>American journal of physiology: endocrinology and metabolism</jtitle><addtitle>Am J Physiol</addtitle><date>1998-11-01</date><risdate>1998</risdate><volume>275</volume><issue>5</issue><spage>E882</spage><epage>E887</epage><pages>E882-E887</pages><issn>0193-1849</issn><issn>0002-9513</issn><eissn>1522-1555</eissn><abstract>Departments of Physiology and Internal Medicine, University of
Michigan, Ann Arbor, Michigan 48109-0622
Insulin attenuates vascular contraction via inhibition of
voltage-operated Ca 2+ channels and
by enhancement of endothelium-dependent vasodilation. Thus it has been
suggested that hypertension-associated insulin resistance results from
an insensitivity to the hormone's effects on vascular reactivity. This
hypothesis has been strengthened by reports that thiazolidinediones, a
class of insulin-sensitizing agents, lower blood pressure and improve
insulin responsiveness in hypertensive, insulin-resistant animal
models. We tested the hypothesis that troglitazone enhances the
vasodilating effect of insulin via inhibition of voltage-operated
Ca 2+ channels in vascular smooth
muscle cells. Rat thoracic aortic rings (no endothelium) were suspended
in tissue baths for isometric force measurement. Rings were incubated
with 0.1 DMSO vehicle (control), troglitazone
(10 5 M), insulin
(10 7 U/l), or both
troglitazone and insulin (1 h) and then contracted with phenylephrine
(PE), KCl, or BAY K 8644. Troglitazone increased the
EC 50 values for PE and KCl.
Contractions to BAY K 8644 in troglitazone-treated rings were virtually
abolished. Insulin alone had no effect on contraction. However, when
insulin was combined with troglitazone, the
EC 50 values for PE and KCl were
further increased. Additionally, the maximum contractions
to both PE (14 ± 4% of control) and KCl (12 ± 2% of control)
were reduced. Measurement of Ca 2+
concentration ([Ca 2+ ])
with fura 2-AM in dispersed vascular smooth muscle cells indicated that
neither insulin nor troglitazone alone altered PE-induced increases in
intracellular [Ca 2+ ].
However, troglitazone and insulin together caused a significant reduction in PE-induced increases in intracellular
[Ca 2+ ] (expressed as
percentage of preincubation stimulation to PE: 47 ± 10%, treated;
102 ± 13%, vehicle). These results demonstrate that troglitazone
inhibits Ca 2+ influx and that it
acts synergistically with insulin to attenuate further vascular
contraction via inhibition of voltage-operated Ca 2+ channels.
vascular smooth muscle; calcium channels</abstract><cop>United States</cop><pmid>9815009</pmid><doi>10.1152/ajpendo.1998.275.5.e882</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0193-1849 |
| ispartof | American journal of physiology: endocrinology and metabolism, 1998-11, Vol.275 (5), p.E882-E887 |
| issn | 0193-1849 0002-9513 1522-1555 |
| language | eng |
| recordid | cdi_highwire_physiology_ajpendo_275_5_E882 |
| source | MEDLINE; American Physiological Society; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology Animals Aorta, Thoracic - drug effects Aorta, Thoracic - physiology Calcium - metabolism Chromans - pharmacology Endothelium, Vascular Hypoglycemic Agents - pharmacology In Vitro Techniques Insulin - pharmacology Isometric Contraction - drug effects Isometric Contraction - physiology Male Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - physiology Phenylephrine - pharmacology Potassium Chloride - pharmacology Rats Rats, Sprague-Dawley Thiazoles - pharmacology Thiazolidinediones Troglitazone Vasodilator Agents - pharmacology |
| title | Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings |
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