In hEDS-associated neuropathic POTS where partial sympathetic denervation of the lower extremity vasculature produces blunted vasoconstriction, blood already pools in peripheral capacitance vessels on standing, stroke volume is structurally reduced, and the sympathetic nervous system is already operating near its compensation ceiling the additional vasodilatory and chronotropic load imposed by chronic dual incretin receptor agonism may have limited physiological reserve to absorb it
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The Gene Modulation Argument The Broad Institute Connectivity Map analysis cited by Campbell et al