Hypertension, Vol 24, 170-175, Copyright © 1994 by American Heart Association
F Zhang, JR Sowers, JL Ram, PR Standley and JD Peuler
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 mumol/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 mumol/L pioglitazone had an
insignificant effect (4.8 +/- 5.6% reduction); however, 25 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Effects of pioglitazone on calcium channels in vascular smooth muscle
Department of Physiology, Wayne State University, School of Medicine, Detroit, MI.
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