ArticleJournal of applied physiology (Bethesda, Md. : 1985)2013
Familial hypercholesterolemia impairs exercise-induced systemic vasodilation due to reduced NO bioavailability.
Article in Journal of applied physiology (Bethesda, Md. : 1985), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- L-Arginine supplementation does not enhance blood flow and muscle performance in healthy and physically active older women.European journal of nutrition · 2016Trial
- Increased cGMP improves microvascular exercise training adaptations in diet-induced obesity.American journal of physiology. Endocrinology and metabolism · 2025Article
- Flaxseed (Nutrients · 2020Article
- Differential impact of severe familial hypercholesterolemia on regional skeletal muscle and organ blood flows during exercise: Effects of PDE5 inhibition.Microcirculation (New York, N.Y. : 1994) · 2019Article
- Endurance exercise training does not limit coronary atherosclerosis in familial hypercholesterolemic swine.Physiological reports · 2019Article
- Severe familial hypercholesterolemia impairs the regulation of coronary blood flow and oxygen supply during exercise.Basic research in cardiology · 2016Article
- Modulation of Hypercholesterolemia-Induced Oxidative/Nitrative Stress in the Heart.Oxidative medicine and cellular longevity · 2016Review
- Myosin phosphatase isoforms and related transcripts in the pig coronary circulation and effects of exercise and chronic occlusion.Microvascular research · 2015Article
- Reduced contribution of endothelin to the regulation of systemic and pulmonary vascular tone in severe familial hypercholesterolaemia.The Journal of physiology · 2014Article
- Impairment of exercise hyperaemia in familial hypercholesterolaemia: complex interplay of vasodilators vs. vasoconstrictors.The Journal of physiology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypercholesterolemia impairs endothelial function [e.g., the nitric oxide (NO)-cyclic GMP-phosphodiesterase 5 (PDE5) pathway], limits shear stress-induced vasodilation, and is therefore expected to reduce exercise-induced vasodilation. To assess the actual effects of hypercholesterolemia on endothelial function and exercise-induced vasodilation, we compared the effects of endothelial NO synthase (eNOS) and PDE5 inhibition in chronically instrumented Yucatan (Control) and Rapacz familial hypercholesterolemic (FH) swine, at rest and during treadmill exercise. The increases in systemic vascular conductance produced by ATP (relative to nitroprusside) and exercise were blunted in FH compared with Control swine. The vasoconstrictor response to eNOS inhibition, with nitro-l-arginine (NLA), was attenuated in FH compared with Control swine, both at rest and during exercise. Furthermore, whereas the vasodilator response to nitroprusside was enhanced slightly, the vasodilator response to PDE5 inhibition, with EMD360527, was reduced in FH compared with Control swine. Finally, in the pulmonary circulation, FH resulted in attenuated vasodilator responses to ATP, while maintaining the responses to both NLA and EMD360527. In conclusion, hypercholesterolemia reduces exercise-induced vasodilation in the systemic but not the pulmonary circulation. This reduction appears to be the principal result of a decrease in NO bioavailability, which is mitigated by a lower PDE5 activity.
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