Pioglitazone attenuates hypertension and inhibits growth of renal arteriolar smooth muscle in rats. Am J Physiol 1993 Oct;265(4 Pt 2):R726-32
Date
10/01/1993Pubmed ID
8238439DOI
10.1152/ajpregu.1993.265.4.R726Scopus ID
2-s2.0-0027443636 (requires institutional sign-in at Scopus site) 143 CitationsAbstract
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.
Author List
Dubey RK, Zhang HY, Reddy SR, Boegehold MA, Kotchen TAMESH terms used to index this publication - Major topics in bold
AnimalsArterioles
Blood Pressure
Cell Division
Epidermal Growth Factor
Hypertension
Hypoglycemic Agents
Insulin
Kidney
Male
Muscle, Smooth
Rats
Rats, Mutant Strains
Rats, Sprague-Dawley
Sodium Chloride
Thiazoles
Thiazolidinediones
Thymidine