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 rosiglitazone 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 microM, respectively. Troglitazone, 2 microM and rosiglitazone, 20 microM caused a similar hyperpolarizing shift of 12 mV in the potential-dependence of Ca2+ current availability. Troglitazone (20 microM) produced a marked block of the tetraethylammonium- and paxilline-sensitive Ca2+ activated K+ current, while rosiglitazone (20 microM and 60 microM) 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 microM), while rosiglitazone caused a smaller inhibition at 10 and 60 microM. 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. reserved.
Knock
G A
GA
Department of Pharmacology, The Guy's, King's College Hospital Medical and Dental School, London, UK.
Mishra
S K
SK
Aaronson
P I
PI
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D002839:Chromans / Q000494:pharmacology*; D004558:Electric Stimulation; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007473:Ion Channels; D015221:Potassium Channels; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077288:Troglitazone