Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings

Cretan Goud, Bertram Pitt, R Clinton Webb, Joyce M. Richey

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Insulin attenuates vascular contraction via inhibition of voltage- operated Ca2+ 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 Ca2+ 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 EC50 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 EC50 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 Ca2+ concentration ([Ca2+]) with fura 2-AM in dispersed vascular smooth muscle cells indicated that neither insulin nor troglitazone alone altered PE-induced increases in intracellular [Ca2+]. However, troglitazone and insulin together caused a significant reduction in PE-induced increases in intracellular [Ca2+] (expressed as percentage of preincubation stimulation to PE: 47 ± 10%, treated; 102 ± 13%, vehicle). These results demonstrate that troglitazone inhibits Ca2+ influx and that it acts synergistically with insulin to attenuate further vascular contraction via inhibition of voltage-operated Ca2+ channels.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume275
Issue number5 38-5
StatePublished - Dec 5 1998

Fingerprint

troglitazone
Endothelium
Insulin
Phenylephrine
Blood Vessels
Vascular Smooth Muscle
Smooth Muscle Myocytes

Keywords

  • Calcium channels
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings. / Goud, Cretan; Pitt, Bertram; Webb, R Clinton; Richey, Joyce M.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 275, No. 5 38-5, 05.12.1998.

Research output: Contribution to journalArticle

@article{9b08e764f8c34be99b7aba82bf6d4cd6,
title = "Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings",
abstract = "Insulin attenuates vascular contraction via inhibition of voltage- operated Ca2+ 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 Ca2+ 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 EC50 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 EC50 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 Ca2+ concentration ([Ca2+]) with fura 2-AM in dispersed vascular smooth muscle cells indicated that neither insulin nor troglitazone alone altered PE-induced increases in intracellular [Ca2+]. However, troglitazone and insulin together caused a significant reduction in PE-induced increases in intracellular [Ca2+] (expressed as percentage of preincubation stimulation to PE: 47 ± 10{\%}, treated; 102 ± 13{\%}, vehicle). These results demonstrate that troglitazone inhibits Ca2+ influx and that it acts synergistically with insulin to attenuate further vascular contraction via inhibition of voltage-operated Ca2+ channels.",
keywords = "Calcium channels, Vascular smooth muscle",
author = "Cretan Goud and Bertram Pitt and Webb, {R Clinton} and Richey, {Joyce M.}",
year = "1998",
month = "12",
day = "5",
language = "English (US)",
volume = "275",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5 38-5",

}

TY - JOUR

T1 - Synergistic actions of insulin and troglitazone on contractility in endothelium-denuded rat aortic rings

AU - Goud, Cretan

AU - Pitt, Bertram

AU - Webb, R Clinton

AU - Richey, Joyce M.

PY - 1998/12/5

Y1 - 1998/12/5

N2 - Insulin attenuates vascular contraction via inhibition of voltage- operated Ca2+ 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 Ca2+ 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 EC50 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 EC50 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 Ca2+ concentration ([Ca2+]) with fura 2-AM in dispersed vascular smooth muscle cells indicated that neither insulin nor troglitazone alone altered PE-induced increases in intracellular [Ca2+]. However, troglitazone and insulin together caused a significant reduction in PE-induced increases in intracellular [Ca2+] (expressed as percentage of preincubation stimulation to PE: 47 ± 10%, treated; 102 ± 13%, vehicle). These results demonstrate that troglitazone inhibits Ca2+ influx and that it acts synergistically with insulin to attenuate further vascular contraction via inhibition of voltage-operated Ca2+ channels.

AB - Insulin attenuates vascular contraction via inhibition of voltage- operated Ca2+ 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 Ca2+ 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 EC50 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 EC50 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 Ca2+ concentration ([Ca2+]) with fura 2-AM in dispersed vascular smooth muscle cells indicated that neither insulin nor troglitazone alone altered PE-induced increases in intracellular [Ca2+]. However, troglitazone and insulin together caused a significant reduction in PE-induced increases in intracellular [Ca2+] (expressed as percentage of preincubation stimulation to PE: 47 ± 10%, treated; 102 ± 13%, vehicle). These results demonstrate that troglitazone inhibits Ca2+ influx and that it acts synergistically with insulin to attenuate further vascular contraction via inhibition of voltage-operated Ca2+ channels.

KW - Calcium channels

KW - Vascular smooth muscle

UR - http://www.scopus.com/inward/record.url?scp=0031760308&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031760308&partnerID=8YFLogxK

M3 - Article

C2 - 9815009

AN - SCOPUS:0031760308

VL - 275

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5 38-5

ER -