Effects of PPAR γ Agonist Pioglitazone on Redox-Sensitive Cellular Signaling in Young Spontaneously Hypertensive Rats.
PPAR γ receptor plays an important role in oxidative stress response. Its agonists can influence vascular contractility in experimental hypertension. Our study was focused on the effects of a PPAR γ agonist pioglitazone (PIO) on blood pressure regulation, vasoactivity of vessels, and redox-sensitive signaling at the central (brainstem, BS) and peripheral (left ventricle, LV) levels in young prehypertensive rats. 5-week-old SHR were treated either with PIO (10 mg/kg/day, 2 weeks) or with saline using gastric gavage. Administration of PIO significantly slowed down blood pressure increase and improved lipid profile and aortic relaxation after insulin stimulation. A significant increase in PPAR γ expression was found only in BS, not in LV. PIO treatment did not influence NOS changes, but had tissue-dependent effect on SOD regulation and increased SOD activity, observed in LV. The treatment with PIO differentially affected also the levels of other intracellular signaling components: Akt kinase increased in the the BS, while β -catenin level was down-regulated in the BS and up-regulated in the LV. We found that the lowering of blood pressure in young SHR can be connected with insulin sensitivity of vessels and that β -catenin and SOD levels are important agents mediating PIO effects in the BS and LV.
Institute of Normal and Pathological Physiology, SAS, Sienkiewiczova 1, 813 71 Bratislava, Slovakia.
Ima
I
Dovinová
Institute for Heart Research, SAS, Dubravska cesta 9, 840 05 Bratislava, Slovakia.
Miroslav
M
Barancik
Institute of Normal and Pathological Physiology, SAS, Sienkiewiczova 1, 813 71 Bratislava, Slovakia.
Miroslava
M
Majzunova
Institute of Experimental Endocrinology, SAS, Vlarska 3, 833 06 Bratislava, Slovakia.
Stefan
S
Zorad
Institute of Experimental Endocrinology, SAS, Vlarska 3, 833 06 Bratislava, Slovakia.
Lucia
L
Gajdosechová
Institute of Normal and Pathological Physiology, SAS, Sienkiewiczova 1, 813 71 Bratislava, Slovakia.
Linda
L
Gresová
Institute of Normal and Pathological Physiology, SAS, Sienkiewiczova 1, 813 71 Bratislava, Slovakia.
Sona
S
Cacanyiova
Institute of Normal and Pathological Physiology, SAS, Sienkiewiczova 1, 813 71 Bratislava, Slovakia.
Frantisek
F
Kristek
Institute of Normal and Pathological Physiology, SAS, Sienkiewiczova 1, 813 71 Bratislava, Slovakia.
Peter
P
Balis
Center for Translational Research in Biomedical Science, Kaohsiung Chang Gang Memorial Hospital, 123 Ta Pei Road, Kaohsiung 83301, Taiwan.
Julie Y H
JY
Chan