Troglitazone and vascular reactivity: Role of glucose and calcium

We sought to determine whether insulin/insulin-like growth factor-1 (IGF-1) and an insulin-sensitizing agent, troglitazone, have additive vasodilatory effects and the possible involvement of intracellular Ca2+ ([Ca2+](i)) and/or glucose utilization in these effects. Contractile responses to norepinephrine [NE) and potassium chloride (KCI), as well as relaxation to endothelium-dependent (acetylcholine [Ach]) and -independent (sodium nitroprusside [NaNP]) agents, were examined in rat tail artery rings in the presence of insulin/IGF-1 and/or troglitazone. Endothelium-intact tail artery rings stretched to 1 g tension were preincubated with troglitazone (3 mu mol/L) and/or insulin/IGF-1 (100 nmol/L) prior to addition of graded doses of NE and KCI. A 90-minute exposure to troglitazone attenuated the maximal contraction to graded doses of NE and KCI (P <.0001). Incubation in glucose-free medium decreased the responses only to NE; troglitazone further attenuated the NE-induced contraction (P =.001). In submaximally precontracted endothelium-intact rings, troglitazone increased the relaxation both to NaNP (P <.0001) and to Ach (P =.001). Contraction experiments in depolarizing KCI (25 mmol/L) or Ca2+-free buffer showed that troglitazone and insulin have a similar Ca2+ dependency. In conclusion, troglitazone, like insulin/IGF-1, attenuates responses to vasoactive agonists through a Ca2+-dependent mechanism that may require the presence of glucose but is independent of insulin action and nitric oxide (NO) production. Copyright (C) 1999 by W.B. Saunders Company.