Regular aerobic exercise reduces endothelin‐1‐mediated vasoconstrictor tone in overweight and obese adults

Abstract

What is the central question of this study? Does aerobic exercise training reduce endothelin-1 (ET-1)-mediated vasoconstrictor tone in overweight/obese adults? And, if so, does lower ET-1 vasoconstriction underlie the exercise-related enhancement in endothelium-dependent vasodilatation in overweight/obese adults? What is the main finding and its importance? Regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight/obese adults, independent of weight loss. Decreased ET-1 vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults. Endothelin-1 (ET-1)-mediated vasoconstrictor tone is elevated in overweight and obese adults, contributing to vasomotor dysfunction and increased cardiovascular disease risk. Although the effects of habitual aerobic exercise on endothelium-dependent vasodilatation in overweight/obese adults have been studied, little is known regarding ET-1-mediated vasoconstriction. Accordingly, the aims of the present study were to determine the following: (i) whether regular aerobic exercise training reduces ET-1-mediated vasoconstrictor tone in overweight and obese adults; and, if so, (ii) whether the reduction in ET-1-mediated vasoconstriction contributes to exercise-induced improvement in endothelium-dependent vasodilatation in this population. Forearm blood flow (FBF) in response to intra-arterial infusion of selective ET receptor blockade (BQ-123, 100 nmol min for 60 min), acetylcholine [4.0, 8.0 and 16.0 μg (100 ml tissue) min ] in the absence and presence of ET receptor blockade and sodium nitroprusside [1.0, 2.0 and 4.0 μg (100 ml tissue) min ] were determined before and after a 3 month aerobic exercise training intervention in 25 (16 men and nine women) overweight/obese (body mass index 30.1 ± 0.5 kg m ) adults. The vasodilator response to BQ-123 was significantly lower (∼25%) and the FBF responses to acetylcholine were ∼35% higher after exercise training. Before the exercise intervention, the co-infusion of acetylcholine plus BQ-123 resulted in a greater vasodilator response than acetylcholine alone; however, after the exercise intervention the FBF response to acetylcholine was not significantly increased by ET receptor blockade. These results demonstrate that regular aerobic exercise reduces ET-1-mediated vasoconstrictor tone in previously sedentary overweight and obese adults. Moreover, decreased ET-1-mediated vasoconstriction is an important mechanism underlying the aerobic exercise-induced improvement in endothelium-dependent vasodilator function in overweight/obese adults.

Endothelin-1 Regulation of Exercise-Induced Changes in Flow: Dynamic Regulation of Vascular Tone

“…ET A and ET A/B receptor antagonism were largely without effect on resting skeletal muscle blood flow in healthy human volunteers, as demonstrated in the forearm and leg with intra-brachial artery ( Cardillo et al, 1999 , 2000 , 2002 , 2004 ; Shemyakin et al, 2006 ; Van Guilder et al, 2007 ; Weil et al, 2011 ; Schreuder et al, 2014 ; Dow et al, 2017 ) and intra-femoral artery infused antagonist, respectively ( Thijssen et al, 2007 ; Barrett-O’Keefe et al, 2013 , 2015 ; Table 2 ). In contrast, other studies demonstrated increased forearm flow with intra-brachial ET A and ET A/B receptor antagonist infusion ( Verhaar et al, 1998 ; Spratt et al, 2001 ; Martin et al, 2002 ; McEniery et al, 2002 ; Table 2 ).…”

“…Another possibility is that undetected endothelial dysregulation is present in otherwise healthy volunteers. Along these lines, ET A /ET A/B receptor antagonism increased forearm resting flow in volunteers with hypercholesterolemia, insulin resistance, type 2 diabetes, excessive weight, and combined excessive weight and hypertension, but not in normal control volunteers ( Cardillo et al, 2000 , 2002 , 2004 ; Mather et al, 2002 ; Shemyakin et al, 2006 ; Weil et al, 2011 ; Dow et al, 2017 ; Table 2 ). Possibly in general support of this explanation is that intra-aorta infused ET A and ET A/B receptor antagonists did not lower blood flow in plantaris, soleus, and tibialis muscle of rats 10 weeks of age ( Maeda et al, 2002 ; Table 1 ).…”

Role of Exercise in Vascular Function and Inflammatory Profile in Age-Related Obesity

“…These alterations are primarily related to a worsening of mitochondrial function, increased inflammatory profile, augmented free radical production, and a gradual loss of antioxidant capacity [ 2 , 3 ]. Altogether, these mechanisms lead to an impairment of nitric oxide (NO) bioavailability [ 1 – 3 ], with reduced endothelium-dependent vasodilation, serving as a risk factor for diabetes, hypertension, dyslipidemia, and several forms of cancer [ 4 ]. Obesity is another condition known to be characterized by vascular dysfunction and, differently from aging, is a reversible state.…”

Efeitos do treinamento físico aeróbio sobre a função sexual em mulheres com síndrome dos ovários policísticos: ensaio clínico controlado

“…Além disso, já foi demonstrado que o treinamento físico aeróbio melhora a função endotelial (BELARDINELLI et al, 2005;DOW et al, 2017). Dessa forma, a melhora de mais escores da função sexual no grupo intermitente, possivelmente ocorreu por uma somatória de fatores, como a redução da RCQ, redução da testosterona, melhora dos escores de ansiedade e depressão e de qualidade de vida, bem como outros fatores não avaliados por este estudo, como VO2máx, o aumento da circulação local e de alteração de fatores metabólicos (ANDERS e HAMPSON, 2005;BELARDINELLI et al, 2005;PALOMBA et al, 2008;TJONNA, A. E. et al, 2008;SIJIE et al, 2012;THOMSON et al, 2012;DE FRÈNE et al, 2015;MATSUO et al, 2015;DOW et al, 2017;GORDON et al, 2017). Esses são fatores bem investigados e avaliados após protocolos de treinamento físico aeróbio, diferente de estudos envolvendo a função sexual.…”

“…O treinamento físico aeróbio intermitente também tem sido demonstrado superior ao treinamento físico aeróbio contínuo em outros estudos e em diferentes variáveis analisadas, como na redução da gordura corporal (MATSUO et al, 2015); no aumento da função endotelial, sinalização da insulina e biogênse no músculo esquelético, na acoplamento excitação-contração e quanto a redução da glicemia (TJONNA, A. E. et al, 2008;DOW et al, 2017), na melhora da bioenergética plaquetária, com o aumento da qualidade mitocondrial, além de diminuir a elevação da geração de trombina mediada por plaquetas, cuja resposta está associada a aliviar a disfunção mitocondrial (WU et al 2017) e na melhora das adaptações hemodinâmicas (TSAI et al, 2016).…”