AJP - Regulatory, Integrative and Comparative Physiology, Vol 265, Issue 4 726-R732, Copyright © 1993 by American Physiological Society
Pioglitazone attenuates hypertension and inhibits growth of renal arteriolar smooth muscle in rats
R. K. Dubey, H. Y. Zhang, S. R. Reddy, M. A. Boegehold and T. A. Kotchen
Department of Medicine, School of Medicine, West Virginia University, Morgantown 26506.
Hypertension is frequently associated with insulin resistance. We evaluated
the effects of pioglitazone, an agent that increases insulin sensitivity,
on the development of hypertension in the Dahl salt-sensitive (Dahl-S) rat
and in the one-kidney, one-clip Sprague-Dawley rat. We also evaluated the
effects of pioglitazone on growth of cultured preglomerular renal
arteriolar smooth muscle cells. In Dahl-S rats fed a 3% NaCl diet, tail
systolic blood pressures and direct arterial pressures were lower (P <
0.05) in pioglitazone-treated (20 mg/kg daily by gavage for 3 wk) than in
control rats (n = 10 rats/group). In one-kidney, one-clip Sprague-Dawley
rats, systolic blood pressures were also lower in pioglitazone-treated
animals (P < 0.0001). In vitro, proliferation of arteriolar smooth
muscle cells was stimulated (P < 0.01) by insulin, epidermal growth
factor (EGF), and fetal calf serum (FCS); pioglitazone (5 microM)
reversibly inhibited (P < 0.01) insulin-, EGF-, and FCS-induced
proliferation. Pioglitazone (0.01-100 microM) also inhibited insulin- (1
mU/ml), EGF- (100 ng/ml), and 5% FCS-induced [3H]thymidine incorporation in
a concentration-dependent manner (P < 0.01). Thus pioglitazone
attenuated the development of hypertension in the Dahl-S rat and the
one-kidney, one-clip rat. The ability of pioglitazone to inhibit growth of
vascular smooth muscle may contribute to its hypotensive effect.
