Effects of Pioglitazone on Calcium Channels in Vascular Smooth Muscle

Pioglitazone, an insulin-sensitizing, antidiabetic agent, has blood pressure-lowering effects in insulin-resistant hypertensive rats and attenuates growth factor-induced increases of intracellular Ca in rat aortic vascular smooth muscle cells. To determine whether modulation of voltagedependent Ca c...

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Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 1994-08, Vol.24 (2), p.170-175
Main Authors: Zhang, Feng, Sowers, James R, Ram, Jeffrey L, Standley, Paul R, Peuler, Jacob D
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Calcium Channels - drug effects
Cells, Cultured
Dimethyl Sulfoxide - pharmacology
General and cellular metabolism. Vitamins
Hypoglycemic Agents - pharmacology
Male
Medical sciences
Muscle, Smooth, Vascular - drug effects
Pharmacology. Drug treatments
Pioglitazone
Rats
Rats, Sprague-Dawley
Thiazoles - pharmacology
Thiazolidinediones
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container_issue 2
container_start_page 170
container_title Hypertension (Dallas, Tex. 1979)
container_volume 24
creator Zhang, Feng
Sowers, James R
Ram, Jeffrey L
Standley, Paul R
Peuler, Jacob D
description Pioglitazone, an insulin-sensitizing, antidiabetic agent, has blood pressure-lowering effects in insulin-resistant hypertensive rats and attenuates growth factor-induced increases of intracellular Ca in rat aortic vascular smooth muscle cells. To determine whether modulation of voltagedependent Ca channels plays a role in this association, we investigated the effects of pioglitazone on voltage-dependent current in cultured rat aortic (a7r5) and freshly dissociated rat tail artery vascular smooth muscle cells. Both cell types were studied with whole-cell patch-clamp techniques. Current through L-type Ca channels was elicited with a voltage ramp in the presence of Ba substituted for Ca. T-type Ca current was studied using a two-pulse protocol that enabled the isolation of transient current. In a7r5 vascular smooth muscle cells, 2-minute application of pioglitazone (5 and 10 μmol/L) reduced L-type current by 7.9±1.0% (n=8) (mean±SEM, number of cells) and 14.5±3.0% (n=9) (P
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To determine whether modulation of voltagedependent Ca channels plays a role in this association, we investigated the effects of pioglitazone on voltage-dependent current in cultured rat aortic (a7r5) and freshly dissociated rat tail artery vascular smooth muscle cells. Both cell types were studied with whole-cell patch-clamp techniques. Current through L-type Ca channels was elicited with a voltage ramp in the presence of Ba substituted for Ca. T-type Ca current was studied using a two-pulse protocol that enabled the isolation of transient current. In a7r5 vascular smooth muscle cells, 2-minute application of pioglitazone (5 and 10 μmol/L) reduced L-type current by 7.9±1.0% (n=8) (mean±SEM, number of cells) and 14.5±3.0% (n=9) (P&lt;.01, two-tailed paired t test), respectively. In contrast, 2-minute application of pioglitazone had no significant effect on T-type Ca current. In freshly dissociated tail artery vascular smooth muscle cells, 2-minute application of 10 μmol/L pioglitazone had an insignificant effect (4.8±5.6% reduction); however, 25 fimolfL pioglitazone reduced L-type current by 27.3 ±7.2% (n=5) (P&lt;.01). Two-minute application of 0.1% or 0.2% dimethyl sulfoxide (vehicle) alone had no significant effects on currents in either type of vascular smooth muscle cell. The blood pressure-lowering and growth-inhibiting effects of pioglitazone may be in part due to inhibition of inward Ca current through L-type channels in vascular smooth muscle.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/01.hyp.24.2.170</identifier><identifier>PMID: 8039840</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Animals ; Biological and medical sciences ; Calcium Channels - drug effects ; Cells, Cultured ; Dimethyl Sulfoxide - pharmacology ; General and cellular metabolism. Vitamins ; Hypoglycemic Agents - pharmacology ; Male ; Medical sciences ; Muscle, Smooth, Vascular - drug effects ; Pharmacology. 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Aug 1994</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5414-c85ae6232f4be4187b0f3e3d89a1e9fc00a187f27a95f34c7abb41e77c20f803</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=4170084$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8039840$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Feng</creatorcontrib><creatorcontrib>Sowers, James R</creatorcontrib><creatorcontrib>Ram, Jeffrey L</creatorcontrib><creatorcontrib>Standley, Paul R</creatorcontrib><creatorcontrib>Peuler, Jacob D</creatorcontrib><title>Effects of Pioglitazone on Calcium Channels in Vascular Smooth Muscle</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><description>Pioglitazone, an insulin-sensitizing, antidiabetic agent, has blood pressure-lowering effects in insulin-resistant hypertensive rats and attenuates growth factor-induced increases of intracellular Ca in rat aortic vascular smooth muscle cells. To determine whether modulation of voltagedependent Ca channels plays a role in this association, we investigated the effects of pioglitazone on voltage-dependent current in cultured rat aortic (a7r5) and freshly dissociated rat tail artery vascular smooth muscle cells. Both cell types were studied with whole-cell patch-clamp techniques. Current through L-type Ca channels was elicited with a voltage ramp in the presence of Ba substituted for Ca. T-type Ca current was studied using a two-pulse protocol that enabled the isolation of transient current. In a7r5 vascular smooth muscle cells, 2-minute application of pioglitazone (5 and 10 μmol/L) reduced L-type current by 7.9±1.0% (n=8) (mean±SEM, number of cells) and 14.5±3.0% (n=9) (P&lt;.01, two-tailed paired t test), respectively. In contrast, 2-minute application of pioglitazone had no significant effect on T-type Ca current. In freshly dissociated tail artery vascular smooth muscle cells, 2-minute application of 10 μmol/L pioglitazone had an insignificant effect (4.8±5.6% reduction); however, 25 fimolfL pioglitazone reduced L-type current by 27.3 ±7.2% (n=5) (P&lt;.01). Two-minute application of 0.1% or 0.2% dimethyl sulfoxide (vehicle) alone had no significant effects on currents in either type of vascular smooth muscle cell. The blood pressure-lowering and growth-inhibiting effects of pioglitazone may be in part due to inhibition of inward Ca current through L-type channels in vascular smooth muscle.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Calcium Channels - drug effects</subject><subject>Cells, Cultured</subject><subject>Dimethyl Sulfoxide - pharmacology</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Pharmacology. 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Vitamins</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Pharmacology. Drug treatments</topic><topic>Pioglitazone</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Thiazoles - pharmacology</topic><topic>Thiazolidinediones</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Feng</creatorcontrib><creatorcontrib>Sowers, James R</creatorcontrib><creatorcontrib>Ram, Jeffrey L</creatorcontrib><creatorcontrib>Standley, Paul R</creatorcontrib><creatorcontrib>Peuler, Jacob D</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 &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Feng</au><au>Sowers, James R</au><au>Ram, Jeffrey L</au><au>Standley, Paul R</au><au>Peuler, Jacob D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Pioglitazone on Calcium Channels in Vascular Smooth Muscle</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>1994-08</date><risdate>1994</risdate><volume>24</volume><issue>2</issue><spage>170</spage><epage>175</epage><pages>170-175</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>Pioglitazone, an insulin-sensitizing, antidiabetic agent, has blood pressure-lowering effects in insulin-resistant hypertensive rats and attenuates growth factor-induced increases of intracellular Ca in rat aortic vascular smooth muscle cells. To determine whether modulation of voltagedependent Ca channels plays a role in this association, we investigated the effects of pioglitazone on voltage-dependent current in cultured rat aortic (a7r5) and freshly dissociated rat tail artery vascular smooth muscle cells. Both cell types were studied with whole-cell patch-clamp techniques. Current through L-type Ca channels was elicited with a voltage ramp in the presence of Ba substituted for Ca. T-type Ca current was studied using a two-pulse protocol that enabled the isolation of transient current. In a7r5 vascular smooth muscle cells, 2-minute application of pioglitazone (5 and 10 μmol/L) reduced L-type current by 7.9±1.0% (n=8) (mean±SEM, number of cells) and 14.5±3.0% (n=9) (P&lt;.01, two-tailed paired t test), respectively. In contrast, 2-minute application of pioglitazone had no significant effect on T-type Ca current. In freshly dissociated tail artery vascular smooth muscle cells, 2-minute application of 10 μmol/L pioglitazone had an insignificant effect (4.8±5.6% reduction); however, 25 fimolfL pioglitazone reduced L-type current by 27.3 ±7.2% (n=5) (P&lt;.01). Two-minute application of 0.1% or 0.2% dimethyl sulfoxide (vehicle) alone had no significant effects on currents in either type of vascular smooth muscle cell. The blood pressure-lowering and growth-inhibiting effects of pioglitazone may be in part due to inhibition of inward Ca current through L-type channels in vascular smooth muscle.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>8039840</pmid><doi>10.1161/01.hyp.24.2.170</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0194-911X
ispartof Hypertension (Dallas, Tex. 1979), 1994-08, Vol.24 (2), p.170-175
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1524-4563
language eng
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subjects Animals
Biological and medical sciences
Calcium Channels - drug effects
Cells, Cultured
Dimethyl Sulfoxide - pharmacology
General and cellular metabolism. Vitamins
Hypoglycemic Agents - pharmacology
Male
Medical sciences
Muscle, Smooth, Vascular - drug effects
Pharmacology. Drug treatments
Pioglitazone
Rats
Rats, Sprague-Dawley
Thiazoles - pharmacology
Thiazolidinediones
title Effects of Pioglitazone on Calcium Channels in Vascular Smooth Muscle
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