Vasodilatory effects of troglitazone improve blood pressure at rest and during mental stress in type 2 diabetes mellitus

The present study examined the hemodynamic mechanisms of blood pressure (BP ) lowering by troglitazone in patients with type 2 diabetes mellitus (DM) a t rest and during a mental arithmetic test (MAT). Twenty-two patients with DM with normal to high-normal BP and 12 controls matched for age,gender, gl ucose tolerance, and BP were studied. DM subjects showed significantly high er systolic BP response during MAT than controls (157 versus 139 mm Hg; P<0 .01). All 22 DM patients and 5 of 12 controls had systolic BP>140 mm Hg dur ing MAT. Heart rate and diastolic BP were not significantly different betwe en the 2 groups. The DM group was then randomized to receive troglitazone ( n=10; 400 mg/d) or glyburide (n=12; 20 mg/d). MAT was repeated after 6 mont hs of treatment. Both treatments reduced glucose equally (-1.7 mmol/L for t roglitazone and -1.5 mmol/L for glyburide), but only troglitazone reduced i nsulin (-15 mu U/mL; P<0.001) and C-peptide (-0.9 ng/mL; P<0.02) levels. Tr oglitazone significantly reduced BP at baseline (P<0.05) and systolic BP re sponse to MAT (P<0.01), whereas glyburide did not affect BP at baseline or during MAT. Stroke volume and cardiac output did not change with either dru g, but troglitazone decreased peripheral vascular resistance (-112 dyne.s.c m(-5); P<0.05). Improved insulin resistance rather than an improved glycemi c control is associated with lower resting and stress BP values in patients with DM. A reduction in vascular resistance may be a primary hemodynamic m echanism of the manner in which troglitazone lowers BP. Insulin sensitizers may offer potential therapeutic advantage in subjects with DM with elevate d BP.