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Differential impact of severe familial hypercholesterolemia on regional skeletal muscle and organ blood flows during exercise: Effects of PDE 5 inhibition
Author(s) -
Aragonez Christian G.,
Beer Vincent J.,
Tharp Darla L.,
Bowles Douglas K.,
Laughlin M. Harold,
Merkus Daphne,
Duncker Dirk J.,
Bender Shawn B.
Publication year - 2019
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12539
Subject(s) - vasodilation , skeletal muscle , medicine , endocrinology , vasomotor , blood flow , vascular smooth muscle , smooth muscle
Abstract Objective Swine with familial hypercholesterolemia ( FH ) exhibit attenuated exercise‐induced systemic vasodilation that is restored by phosphodiesterase 5 ( PDE 5) inhibition. Whether the impacts of FH and PDE 5 inhibition to impair and restore exercise‐induced vasodilation, respectively, results from tissue‐specific or generalized effects remains unclear. Thus, we hypothesized that FH induces generalized impairment of skeletal muscle vasodilation that would be alleviated by PDE 5 inhibition. Methods Systemic vascular responses to exercise were assessed in chronically instrumented normal and FH swine before and after PDE 5 inhibition with EMD 360527. Skeletal muscle and organ blood flows and conductances were determined via the microsphere technique. Results As previously reported, vs normal swine, FH swine have pronounced elevation of total cholesterol and impaired exercise‐induced vasodilation that is restored by PDE 5 inhibition. Blood flows to several, not all, skeletal muscle vascular beds were severely impaired by FH associated with reduced blood flow to many visceral organs. PDE 5 inhibition differentially impacted skeletal muscle and organ blood flows in normal and FH swine. Conclusions These data indicate that FH induces regional, not generalized, vasomotor dysfunction and that FH and normal swine exhibit unique tissue blood flow responses to PDE 5 inhibition thereby adding to accumulating evidence of vascular bed‐specific dysfunction in co‐morbid conditions.