Effects of aerobic exercise training on metabolism of nitric oxide and endothelin-1 in lung parenchyma of rats with pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and proliferative obstruction of pulmonary vessels, which promotes a progressive increase in pulmonary vascular resistance (PVR). The effect of exercise training on oxidative stress, metabolism, and markers of nitric oxide (NO) and endothelin-1 (ET-1) was analyzed in the lung tissue of rats with PAH induced by monocrotaline (MCT).Twenty-four Wistar rats were divided into four groups (5-7 animals): sedentary control (SC), sedentary MCT (SM), trained control (TC), and trained MCT (TM). The TC and TM groups participated in a treadmill training protocol (60% VO max) for 5 weeks, 3 weeks of which were performed after the injection of MCT (60 mg/kg i.p.) or saline. MCT administration promoted an increase in PVR and right ventricle hypertrophy, and reduction of right ventricle systolic function assessed by echocardiography. These changes were not improved by exercise training. The activity of NO synthase was reduced in the animals of the TC, TM, and SM groups. No significant differences were found in total nitrite concentration and expression of endothelial NO synthase. Moreover, the TM group showed strong staining for iNOS and nitrotyrosine, suggesting an increase in oxidative stress in these animals. In parallel, reduced expression of type B ET-1 receptors was noticed in the SM and TM groups in comparison to controls. In conclusion, the aerobic training protocol was unable to mitigate changes in the metabolism of NO and ET-1, probably because of the disease severity in these animals, especially in the TM group.

Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response

“…The expression of MCP-1 increases in several types of PAHs, and the level of MCP-1 in circulation is correlated with disease severity [ 44 ]. Furthermore, NF-kB regulates MCP-1 in vascular smooth muscle cells [ 45 ].…”

Cardioprotection in right heart failure

“…Exercise increases the expression and phosphorylation of AMPK (Musi et al, 2005). Activation of AMPK pathways (by metformin) was sufficient to attenuate RV failure in two pulmonary hypertension models indicating existence of this protective pathway in left and right ventricular tissues (Zhai et al, 2018). Furthermore, AMPK improves ischaemic substrate metabolism and reduces infarct size (Pons et al, 2013).…”

Mechanisms underlying the impact of exercise training in pulmonary arterial hypertension

“…No vasodilatory shift of the NOS/sGC/PDE enzyme expression was observed after exercise training, despite the decrease in small pulmonary vessel muscularization [42]. Also, 3 weeks of treadmill running post-MCT injection had no beneficial effect on lung NO and ET-1 metabolism [47]. Curiously, acute [34] and chronic high-intensity interval training (but not moderate continuous training) [46] increased lung eNOS expression, suggesting that intensity may be an important factor for lung eNOS activation.…”

“…In the majority of the studies, exercise training showed beneficial effects on cardiac remodelling [34,[36][37][38][40][41][42][43][44][45][46]48]. Still, others reported no improvement [47,49] or aggravation [50]. From those that studied the molecular changes associated with exercise training, mediators related with proliferation, apoptosis, oxidative stress, inflammation and proteolysis were evaluated, given the relevance of these processes in RV adaptation to PAH [51,52].…”