Differential effects of insulin-sensitizers troglitazone and rosiglitazone on ion currents in rat vascular myocytes

Insulin-sensitizing thiazolidinediones such as troglitazone and pioglitazone have been shown to lower blood pressure in vivo and cause vasorelaxation in vitro. Rosiglitazone (BRL 49653) is a novel thiazolidinedione which has been reported not to cause vasoleraxation. We therefore compared the effects of troglitazone and rosglitazone on Ca2+ and K+ currents in rat aorta and pulmonary artery smooth muscle cells. Currents were recorded with the conventional whole cell patch clamp technique. Both drugs reduced the voltage-gated (L-type) Ca2+ current in rat aorta cells, with half-maximal current inhibition by troglitazone and rosiglitazone at 2 and 10 mu M: respectively. Troglitazone, 2 mu M and rosiglitazone, 20 mu M caused a similar hyperpolarizing shift of 12 mV in the potential-dependence of Ca2+ current availability. Troglitazone (20 mu M) produced a marked block of the tetraethylammonium- and paxilline-sensitive Ca2+ activated K+ current, while rosiglitazone (20 mu M and 60 mu M) slightly enhanced this current. Rat pulmonary artery smooth muscle cells have a prominent delayed rectifier K+ current. Troglitazone produced a potent block of this current (half-maximal inhibition at < 1 mu M), while rosiglitazone caused a smaller inhibition at 10 and 60 mu M. These results show that troglitazone has relatively potent blocking effects on a wide variety of ion currents in vascular smooth muscle cells. Rosiglitazone exerts less potent, but similar effects on the Ca2+ current and delayed rectifier K+ current, but it enhances the Ca2+-activated K+ current. (C) 1999 Elsevier Science B.V. All rights reserved.