title: Pioglitazone attenuates hypertension and inhibits growth of renal arteriolar smooth muscle in rats.
abstract: 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.
authors.affiliation: Department of Medicine, School of Medicine, West Virginia University, Morgantown 26506.
authors.forename: R K
authors.initials: RK
authors.lastname: Dubey
authors.forename: H Y
authors.initials: HY
authors.lastname: Zhang
authors.forename: S R
authors.initials: SR
authors.lastname: Reddy
authors.forename: M A
authors.initials: MA
authors.lastname: Boegehold
authors.forename: T A
authors.initials: TA
authors.lastname: Kotchen
mesh_terms: D000818:Animals; D001160:Arterioles / Q000166:cytology* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006973:Hypertension / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology* / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D013936:Thymidine / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D012965:Sodium Chloride; D004815:Epidermal Growth Factor; D013936:Thymidine; D000077205:Pioglitazone