ROSIGLITAZONE AND PIOGLITAZONE PROTECT FROM INSULIN RESISTANCE-INDUCED HYPERTENSION INDEPENDENT OF THEIR INSULIN SENSITIZING ACTIVITY

Perixosome proliferator-activated receptor ɣ( PPAR ɣ) Is a key regulator of glucose homeostasis and adipogenesis. In the present Study. we investigated the protective effect of PPAR ɣ Simulation from the hypertension associated with insulin resistance Insulin resistance  (IR) was induced n rats by fructose (10%. in drinking Water) and rats were left for 12weeks for development of vascular dysfunction. Two PPAR ɣ agonists were daily administered in the last 6 weeks of study, pioglitazone (10 mg.kg ¹), rosiglitazone (5 mg. kg^-1). The. blood pressure (BP) was recorded and serum levels of glucose, insulin and lipids were measured. Rings of thoracic aorta were used to measure responses to phenylephrine (PE). KCI. acetylcholine (ACh). Ca²⁺ influx. reactive oxygen species (ROS) and nitric oxide (NO).
IR was associated with elevation in systolic and diastolic BP while, both PPAR ɣ stimulants significantly reduced the elevation in diastolic BP. PPAR ɣ stimulants decreased elevated scrum insulin level in IR but serum insulin is not correlated with diastolic BP. IR increased vasoconstriction response of aorta to PEl and KCI. decreased vasorelaxation response to ACh while PPAR ɣ Stimulants prevented the exaggerated response to PE and KCI but not affected response to ACh. IR increased KCI-induced Ca²⁺ influx while PPAR ɣ stimulation restored normal Ca²⁺ influx. IR was accompanied with elevated levels of AGES. triglycerides. total and LDL cholesterol while PPAR ɣ stimulants normalized these levels.
conclusion, PPAR ɣ stimulation protects from the insulin resistance induced elevation m Bp through a mechanism  involving  prevention of exaggerated vascular contractility.