Effects of ciglitazone on blood pressure and intracellular calcium metabolism.
Ciglitazone is the prototype of the thiazolidinedione class of compounds currently being developed for the treatment of insulin resistance and non-insulin-dependent diabetes. The effects of thiazolidinediones on blood pressure and cell calcium metabolism are not well defined. In the obese Zucker rat, a widely studied model of insulin resistance associated with mild hypertension, we investigated the effects of ciglitazone on plasma insulin levels and mean arterial pressure. We also evaluated the effects of ciglitazone on the changes in cytosolic calcium induced by platelet-derived growth factor in A172 human glioblastoma cells and rat A10 vascular smooth muscle cells. Oral administration of ciglitazone, approximately 45 mg/kg per day for 4 weeks, induced significant reductions in plasma insulin levels (p < 0.001) and blood pressure (p < 0.05). Ciglitazone was also found to significantly attenuate the capacity of platelet-derived growth factor BB homodimer to induce sustained increases in intracellular free calcium. These findings suggest that thiazolidinediones may offer a novel pharmacological approach to the treatment of hypertension, and raise the possibility that these compounds may affect blood pressure not only by affecting insulin metabolism but also by modifying the cell calcium response to pressor agents, growth factors, or both.
Pershadsingh
H A
HA
Department of Family Practice, Kern Medical Center, Bakersfield, Calif.
Szollosi
J
J
Benson
S
S
Hyun
W C
WC
Feuerstein
B G
BG
Kurtz
T W
TW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D007328:Insulin / Q000097:blood; D007425:Intracellular Membranes / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014407:Tumor Cells, Cultured / Q000378:metabolism
D007328:Insulin; D010982:Platelet-Derived Growth Factor; D013844:Thiazoles; D045162:Thiazolidinediones; D002118:Calcium; C039671:ciglitazone