Effects of pioglitazone on calcium channels in vascular smooth muscle

Feng Zhang, James R. Sowers, Jeffrey L. Ram, Paul R. Standley, Jacob D. Peuler

Research output: Contribution to journalArticle

128 Scopus citations

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 Ca2+ in rat aortic vascular smooth muscle cells. To determine whether modulation of voltage-dependent Ca2+ 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 Ca2+ channels was elicited with a voltage ramp in the presence of Ba2+ substituted for Ca2+. T-type Ca2+ 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<.01, two-tailed paired t test), respectively. In contrast, 2-minute application of pioglitazone had no significant effect on T-type Ca2+ 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 μmol/L pioglitazone reduced L-type current by 27.3±7.2% (n=5) (P<.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 Ca2+ current through L-type channels in vascular smooth muscle.

Original languageEnglish (US)
Pages (from-to)170-175
Number of pages6
JournalHypertension
Volume24
Issue number2
DOIs
StatePublished - Aug 1994
Externally publishedYes

Keywords

  • calcium channels
  • insulin
  • muscle, smooth, vascular
  • thiazoles

ASJC Scopus subject areas

  • Internal Medicine

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