%0 Journal Article
%T Effects of PPAR¦Ă Agonist Pioglitazone on Redox-Sensitive Cellular Signaling in Young Spontaneously Hypertensive Rats
%A Ima Dovinov¨˘
%A Miroslav Barancik
%A Miroslava Majzunova
%A Stefan Zorad
%A Lucia Gajdosechov¨˘
%A Linda Gresov¨˘
%A Sona Cacanyiova
%A Frantisek Kristek
%A Peter Balis
%A Julie Y. H. Chan
%J PPAR Research
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/541871
%X PPAR¦Ă 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¦Ă 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 (10Łżmg/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¦Ă 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 ¦Â-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 ¦Â-catenin and SOD levels are important agents mediating PIO effects in the BS and LV. 1. Introduction Blood pressure is regulated by several internal systems. Power-spectral analysis identifies oscillations in heart rate and blood pressure that are modulated by inputs from the renin-angiotensin system, sympathetic and parasympathetic neurons, and locally released vasoactive factors such as nitric oxide (NO). Current findings support the view that the reactive oxygen species (ROS) and antioxidant enzymes such as superoxide dismutase (SOD) expressed in the central nervous system (CNS) play an important role in the regulation of blood pressure, and perturbations in redox homeostasis contribute to pathogenesis of hypertension [1]. Activity of ROS sources (such as NADPH oxidases), stimulated through angiotensin II system and AT1 receptors are involved in redox-sensitive intracellular signaling modulated by kinase cascades and transcriptional factors in cardiovascular system [2]. Antioxidant response and the potential sites of internal antioxidants of different SOD isoforms, could modulate blood pressure in the vasculature, the brain, and the kidney [1, 2]. The peroxisome proliferator-activated receptor ¦Ă (PPAR¦Ă) is a nuclear receptor that takes part in the regulation of lipid metabolism and in cellular signaling. Dysregulation in the PPAR¦Ă activity may
%U http://www.hindawi.com/journals/ppar/2013/541871/