Statin Therapy Enhances Reflex Cutaneous Vasodilation in Formerly Hypercholesterolemic Older Adults by Improving Neurovascular Coupling

Abstract

Reflex cutaneous vasodilation is attenuated in healthy human aging and is mediated by alterations in both central (sympathetic outflow) and peripheral (microvascular endothelial) function. Hypercholesterolemia, a primary risk factor for cardiovascular disease, is associated with increased sympathetic nervous system activity and further impairments in endothelial function. Independent of their lipid‐lowering effect, HMG‐CoA reductase inhibitors (statins) – the most commonly prescribed medication in the U.S. – reduce sympathetic outflow and augment endothelium‐dependent dilation. However, whether statin therapy improves the relation between skin sympathetic nervous system activity (SSNA) and cutaneous vascular conductance (CVC) during passive heat stress is unknown. We hypothesized that (1) hypercholesterolemic older adults would demonstrate blunted increases in both SSNA and CVC during passive heating and (2) chronic statin treatment would improve the response range and sensitivity of the SSNA:CVC relation. Reflex vasodilation was induced in 13 healthy normocholesterolemic older adults [62±2 yrs; low‐density lipoprotein (LDL) 113±7 mg/dl), 10 hypercholesterolemic older adults (60±1 yrs; LDL 183±2 mg/dl), and 10 previously hypercholesterolemic older adults now treated with a lipophilic statin (10–40 mg daily) to normalize LDL (64±1 yrs; LDL 102±2 mg/dl) using a water‐perfused suit to elevate oral temperature (Tor) by 1.0°C. SSNA (peroneal microneurography) and red cell flux (laser Doppler flowmetry) in the innervated dermatome (the dorsum of foot) were continuously measured. SSNA was normalized to, and expressed as, a percentage of baseline and CVC was calculated as flux/mean arterial pressure and expressed as a percentage of maximal CVC (local heating to 43°C). Mean arterial pressure, baseline CVC, and maximal CVC were not significantly different among groups (all p>0.05). During passive heating, the increase in SSNA was not different among groups (normal: Δ=393±96%, high: Δ=311±120%, and statin: Δ=256±90%; p=0.11). Reflex vasodilation was blunted in hypercholesterolemic adults, but not in statin‐treated adults, compared to normocholesterolemic adults (normal: 36±1%CVCmax, high: 32±1%CVCmax, and statin: 38±1%CVCmax respectively, at ΔTor=1.0°C; p<0.01). There were no differences among groups for the slope of the ΔSSNA:ΔCVC relation (normal: 0.06±0.00, high: 0.07±0.01, and statin: 0.07±0.01, p=0.91); however, this relation was shifted upward in statin‐treated adults (y‐intercept; normal: 3.1±0.9, high: 4.0±0.9, and statin: 7.3±1.3; p=0.001). These data demonstrate that chronic statin treatment improves reflex cutaneous vasodilation in formerly hypercholesterolemic older adults, in part via increases in end‐organ responsiveness to sympathetic outflow during passive heat stress.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.