Vasculo-protective effects of insulin sensitizing agent pioglitazone in neointimal thickening and hypertensive vascular hypertrophy

A novel insulin sensitizing agent, thiazolidine, has been demonstrated to i nhibit the growth of cultured vascular smooth muscle cells (VSMC) in vitro. This study was undertaken to examine the in vivo effects of the thiazolidi ne compound pioglitazone (PIO) on carotid neointimal thickening, after endo thelial injury in Wistar rats and vascular hypertrophy in stroke-prone spon taneously hypertensive rats (SHR-SP/Izm). PIO treatment (3 mg/kg/day for 1 week prior to endothelial injury and 2 weeks postendothelial injury) remark ably decreased neointimal cross-sectional areas in treated animals (63.8 +/ - 4.9 x 10(3) mu m(2)) versus controls (196 +/- 7.6 x 10(3) mu m(2), P < 0. 05). Bromodeoxyuridine uptake in the neointima, a marker of DNA synthesis, was also decreased after treatment compared with controls. In SHR-SP/Izm bu t not in Wistar rats, PIO treatment decreased blood pressure and plasma ins ulin levels. PIO treatment in SHR-SP/Izm (3 mg/kg/day from 4 weeks of age f or 7 weeks) significantly decreased the medial wall thickness of the mesent eric artery (10.4 +/- 1.2 x 10(3) mu m(2) versus control, 21.2 +/- 2.4 x 10 (3) mu m(2), P < 0.05). In addition, PIO treatment significantly decreased the expression of EIIIA fibronectin both in the carotid neointima of Wistar rats and the media of the mesenteric artery in SHR-SP/Izm compared with th eir respective controls (P < 0.05). These results suggest that PIO has vasc ulo-protective effects in both acute and chronic vascular injury in vivo th rough inhibition of VSMC proliferation. (C) 1999 Elsevier Science Ireland L td. All rights reserved.