Evaluation of the influence of perivascular adipose tissue on the vascular reactivity of the aorta of rats with heart failure submitted to aerobic and resistance training.

Author(s)

Milene Tavares Fontes

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2019-02-15

Examining board members

Luciana Venturini Rossoni; Eliana Hiromi Akamine; Kátia de Angelis Lobo D'Avila; Ana Paula Couto Davel; Jose Geraldo Mill

• Advisor: Luciana Venturini Rossoni

Abstract

Perivascular adipose tissue (PVAT) releases dilating and constricting substances, and the dilators overlap, exerting an anti-contractile effect. This effect is impaired in the presence of some cardiovascular diseases. In heart failure (HF) damage to the vascular system occurs, however, no study has evaluated the function of PVAT in HF. The use of physical training (PT) has been recommended with non-pharmacological therapy effective in promoting cardiovascular system benefits. The recommendations suggest that resistance exercise be added to the PT programs for patients with HF, thus, combined training (CT, aerobic and resisted) may provide additional cardiovascular health benefits. The objective of the present study was to evaluate the role of PVAT in the vascular reactivity of the thoracic aorta of HF rats and, after that, to evaluate the influence of CT in the anti-contractile response of PVAT of the thoracic and abdominal aorta of healthy and HF rats. Wistar rats were submitted to descending coronary artery occlusion or false operated (SO). After 4 weeks, for the study without CT, the animals were kept without intervention, and for the study involving the CT were divided into sedentary (SOs and HFs) and trained (SOt and HFt, treadmill and ladder, 5 x/8 sem.). In the presence (PVAT+) or in the absence of the PVAT (PVAT-), thoracic and/or abdominal aorta with (E+) and without endothelium (E-), were mounted on wire myograph and concentration-response curves to phenylephrine, (PHE, 10-9-10-5M) were performed. HF promoted an increase in PHE contraction in the E+/PVAT- rings of the thoracic aorta when compared to SO, and the ani-contratile effect of PVAT was impaired by HF in the E+/PVAT+ and E-/PVAT+ rings. The impairment in the anti-contratile effect of PVAT was accompanied by increased activity of ECA1 and the expression of AT1R, AT2R and MASR in the PVAT of animals with HF. The AT1R, AT2R and MASR antagonism promoted a reduction of the contractile response in the E+/PVAT- rings in the HF, in the E+/PVAT+ rings, this reduction was superior only to the antagonism of AT1R and AT2R. The production of reactive oxygen species (ROS) in the thoracic aorta and PVAT of the HF animals was higher than in the SO, accompanied by a lower NO bioavailability. CT increased physical capacity in SOt and HFt. In the thoracic aorta CT reversed part of the impairment of PVAT anti-contratile function, increased the expression of PRDM-16 and ESPST-1 that were reduced in HF, in addition, it improved the bioavailability of NO in PVAT by the greater expression of eNOS, β3-AR and AMPk1/2 α, increased the concentration of adiponectin and reduced proinflammatory markers. In the abdominal aorta, the anti-contratile effect of PVAT was not present and CT reversed the endothelial dysfunction of HF animals, increasing NO bioavailability and eNOS expression in the aorta. In conclusion, in HF, AT1R and AT2R contribute to both endothelial and PVAT dysfunction, reducing NO bioavailability and increasing ROS production. CT improved the anti-contractile function in the thoracic aorta due to benefits in the β3-AR/Adiponectin/AMPK/eNOS signaling pathway, modifying the morphological and inflammatory profile of PVAT. Already in the abdominal aorta, the CT improved the vascular function, the CT improved the vascular function, increasing the bioavailability of NO. (AU)

• FAPESP's process: 14/20303-0 - Evaluation of the influence of perivascular adipose tissue (PVAT) on vascular reactivity of the aorta of infarcted rats submitted to aerobic and resistance training
• Grantee: Milene Tavares Fontes
• Support Opportunities: Scholarships in Brazil - Doctorate