Cardiology Letters 2020, 29(2):113-120

Effect of sub-chronic administration of pioglitazone on blood pressure and endothelial function in borderline hypertensive rats: the role of nitric oxide

Kvandová M¹, Bališ P², Púzserová A², Dovinová I^{2, 3}

¹ Center for Cardiology I, Molecular Cardiology, University Medical Center, Mainz, Germany

² Centrum experimentálnej medicíny Slovenskej akadémie vied, Ústav normálnej a patologickej fyziológie, Bratislava

³ Ústav biochémie a mikrobiológie, Fakulta chemickej a potravinárskej technológie, Slovenská technická univerzita, Bratislava, Slovenská republika

Aim: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent intracellular protein and interest in its activation has risen over recent years, considering its influence on hypertension development. The aim of this study was to investigate the effect of sub-chronical activation of PPARγ by the exogenous agonist - pioglitazone on blood pressure, activity of nitric oxide synthase (NOS), superoxide production (O2*-) and on the functional status on the endothelium of small resistant arteries in experimental borderline hypertensive rats (BHR).

Methods: Young (5 weeks) and adult (12 weeks) male borderline hypertensive rats (BHR) were used. Pioglitazone was administered intragastrically at a dose of 10 mg/kg/day over ten days. The pulse frequency (PF) and systolic blood pressure (sBP) were detected using plethysmography. The superoxide production (O2*-) was determined using chemiluminescence and NOS activity by a method using the conversion of radioactive [3H] L-arginine to [3H] L-citrulline. Vascular reactivity of resistant mesenteric arteries was monitored in vitro using Mulvany wire myograph under isometric conditions.

Results: Pioglitazone treatment decreased sBP in young BHR and in adult BHR, and we observed a decreased sBP by trend. PPARγ activation reduced PF in both young and adult BHR. In the heart, administration of pioglitazone increased the total enzyme activity of NOS in adult BHR, and similarly, we observed a decreased production of O2*- in adult BHR animals. In young animals, no changes in these parameters in the left heart ventricle were observed. In the aorta, O2*- production was decreased in both young and adult BHR, although the enzyme activity of NOS was not changed by PPARγ activation. We observed a slightly improved endothelium-dependent acetylcholine-induced relaxation response of a. mesenterica in both young and adult BHR after pioglitazone treatment. Nevertheless the maximal vasorelaxing response was not affected.

Conclusion: In conclusion, pioglitazone-dependent activation of PPARγ may contribute to BP regulation and thus affect the progression of hypertension through modulation of redox regulation and increased nitric oxide bioavailability. Although the nuclear receptor PPARγ plays a primarily key role in the energy metabolism regulation, our results suggest that it may be a potential therapeutic target for the influencing of increased blood pressure as well.

Keywords: PPARγ; NOS; superoxide; hypertension; vascular endothelium

Published: February 1, 2020  Show citation