Pioglitazone improves superoxide dismutase mediated vascular reactivity in the obese Zucker rat.
OBJECTIVE
To test the hypothesis that the thiazolidinedione agent, pioglitazone, mediates its chronic BP lowering action via improving vascular reactivity.


RESULTS
Lean (Fa/fa) and obese (fa/fa) Zucker rats were treated with or without pioglitazone (20 mg/ kg/day) for 4 weeks (n=8 animals per group). Pioglitazone treatment was associated with a significant improvement in oral glucose tolerance in the obese animals (p<0.05 compared with untreated obese). Pioglitazone prevented the development of hypertension seen in obese untreated rats (SBP 126+/-1 versus 138+/-1 mmHg; p<0.0001). Aortic ring preparations from pioglitazone-treated obese rats showed improved relaxation responsiveness (ED(50) 0.28 versus 1.15 U/ ml, p<0.001) to SOD, a NO potentiator, compared with untreated obese animals.


CONCLUSIONS
SOD-mediated vasorelaxation may contribute to the chronic antihypertensive effect and/or the improvement in insulin sensitivity following pioglitazone treatment.
Dorafshar
Amir H
AH
Department of Medicine, University of California Los Angeles, California, USA.
Moodley
Kogie
K
Khoe
Michelle
M
Lyon
Chris
C
Bryer-Ash
Michael
M
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D005951:Glucose Tolerance Test; D006973:Hypertension / Q000378:metabolism / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000517:prevention & control*; D009599:Nitroprusside / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D000077205:Pioglitazone; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D013482:Superoxide Dismutase / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D011189:Potassium Chloride; D013482:Superoxide Dismutase; D000109:Acetylcholine; D000077205:Pioglitazone