| Full text | |
| Author(s): |
Couto, Gisele K.
[1]
;
Paula, Suliana M.
[1]
;
Gomes-Santos, Igor L.
[2]
;
Negrao, Carlos Eduardo
[3, 2]
;
Rossoni, V, Luciana
Total Authors: 5
|
| Affiliation: | [1] V, Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Prof Linea Prestes Ave 1524, Rm 225, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Heart Inst InCor HCFMUSP, Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 314, n. 4, p. H878-H887, APR 2018. |
| Web of Science Citations: | 6 |
| Abstract | |
Exercise training (ET) has emerged as a nonpharmacological therapy for cardiovascular diseases because of its helpful milieu for improving vascular function. The aim of the present study was to assess whether ET reverses the alterations in vascular reactivity observed in heart failure (HF)-related coronary arteries and to elucidate the molecular mechanisms involved in these adjustments. Male Wistar rats were subjected to either coronary artery ligation or sham operation. Four weeks after the surgery, rats were divided into two groups: untrained HF (UHF) and exercise-trained HF (THF). ET was conducted on a treadmill for 8 wk. An untrained SO group was included in the study as a normal control. ET restored the impaired acetylcholine (ACh)-and sodium nitroprusside-induced relaxation in coronary arteries to levels of the control. Oxidative stress and reduced nitric oxide (NO) production were observed in UHF, whereas ET restored both parameters to the levels of the control. Expression levels of endothelial NO synthase (eNOS) and soluble guanylyl cyclase subunits were increased in coronary arteries of UHF rats but reduced in THF rats. Tetrahydrobiopterin restored ACh-induced NO production in the UHF group, indicating that eNOS was uncoupled. ET increased the eNOS dimer-to-monomer ratio and expression of GTP cyclohydrolase 1, thus increasing NO bioavailability. Taken together, these findings demonstrate that ET reverses the dysfunction of the NO/soluble guanylyl cyclase pathway present in coronary arteries of HF rats. These effects of ET are associated with increased GTP cyclohydrolase 1 expression, restoration of NO bioavailability, and reduced oxidative stress through eNOS coupling. NEW \& NOTEWORTHY The present study provides a molecular basis for the exercise-induced improvement in coronary arteries function in heart failure. Increasing the expression of GTP cyclohydrolase 1, the rate-limiting enzyme in the de novo biosynthesis of tetrahydrobiopterin, exercise training couples endothelial nitric oxide synthase, reduces oxidative stress, and increases nitric oxide bioavailability and sensitivity in coronary arteries of heart failure rats. (AU) | |
| FAPESP's process: | 10/50048-1 - Cellular and functional bases of exercise in cardiovascular diseases |
| Grantee: | Carlos Eduardo Negrão |
| Support Opportunities: | Research Projects - Thematic Grants |