Effect of pioglitazone on vascular reactivity in vivo and in vitro
( pioglitazone and vascular reactivity).
Kotchen, Theodore A., Hong Yan Zhang, Sreenivas Reddy, Raymond G.
Hoffmann.
Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
53226
APStracts 2:0309R, 1995.
Pioglitazone (a thiazolidinedione derivative) increases insulin
sensitivity and prevents hypertension in the Dahl-salt sensitive (S)
rat. The present study was undertaken to determine if pioglitazone
modulates pressor responsiveness to vasoactive agents, both in vivo
and in vitro. In vivo, pre-treatment with pioglitazone inhibited
(p< 0.02) pressor responses to both norepinephrine and
angiotensin II in conscious Dahl-S, but not in Sprague Dawley rats.
In vitro, pioglitazone augmented the capacity of insulin to inhibit
pressor responses of strips of thoracic aortae to norepinephrine, but
not to angiotensin. Additionally, in vitro, incubation with insulin
plus pioglitazone augmented acetylcholine-induced, but not
nitroprusside-induced vasodilation. Pioglitazone pre-treatment
increased (p< 0.001) in vitro insulin stimulated glucose uptake
in adipose tissue, but not in thoracic aortae of Dahl-S. We
hypothesize that pioglitazone attenuates hypertension by modulating
the effects of insulin on vascular function, resulting in both
blunted vasoconstriction and augmented acetylcholine-induced
vasodilation. These alterations are not accounted for by an effect of
pioglitazone on glucose uptake by vascular smooth muscle.
Received 5 July 1995; accepted in final form 23 October 1995.
APS Manuscript Number R417-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95