Chronic statin therapy is associated with enhanced cutaneous vascular responsiveness to sympathetic outflow during passive heat stress.
Chronic statin therapy is associated with enhanced cutaneous vascular responsiveness to sympathetic outflow during passive heat stress.
复制标题
慢性他汀类药物治疗与被动热应激期间皮肤血管对交感神经流出的反应性增强有关。
DOI：
10.1113/jp278237
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kenney,WLarry
中科院分区：
文献类型：
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作者：
Greaney,JodyL;Stanhewicz,AnnaE;Kenney,WLarry
健康老年人热应激时，中枢性交感神经和外周微血管功能损伤导致反射性皮肤血管舒张减弱。高胆固醇血症与神经血管功能下降有关；然而，人们对高胆固醇血症对热应激综合反应的影响知之甚少。此外，慢性他汀类药物治疗是否会改变热应激时皮肤交感神经流出或其与皮肤血管传导的关系尚不清楚。我们证明，与年龄匹配的对照组相比，年龄较大的高胆固醇血症成人的反射性皮肤血管舒张功能受损，但目前接受他汀类药物治疗的既往高胆固醇血症成人的反射性皮肤血管舒张功能没有受损。此外，慢性他汀类药物治疗引起的反射性血管舒张的改善，部分是通过全身加热时终端器官对传出交感神经流出的反应性增加来介导的。这些数据增加了越来越多的文献，证实了慢性他汀类药物治疗有益的多效神经血管作用，并进一步支持他汀类药物在老年人中具有额外的心脏保护作用。摘要健康人衰老过程中反射性皮肤血管舒张减弱是由中枢（交感神经流出）和外周（微血管内皮）功能的改变介导的。高胆固醇血症与神经血管功能的进一步损害有关。HMG - CoA还原酶抑制剂（他汀类药物）改善皮肤内皮依赖性扩张；然而，他汀类药物治疗是否会改变被动热应激时皮肤交感神经系统活动（SSNA）或其与皮肤血管传导（CVC）的关系尚不清楚。我们假设(1)高胆固醇血症的老年人在被动加热时SSNA和CVC的增加会减弱，(2)慢性他汀类药物治疗会改善SSNA:CVC关系的反应范围和敏感性。在13例正常胆固醇血症的健康成人（62±2岁，LDL = 113±7 mg/dl）、10例高胆固醇血症的成人（60±1岁，LDL = 183±2 mg/dl）和10例既往高胆固醇血症的成人（64±1岁，LDL = 102±2 mg/dl）中，采用亲脂性他汀类药物（每天10 - 40 mg），诱导了1.0°C口腔温度升高（Tor；水灌注服）后的反射性血管舒张。连续测量受神经支配的皮节（足背）的SSNA（腓骨微神经摄影）和红细胞通量（激光多普勒血流仪）。与正常胆固醇血症的成年人相比，高胆固醇血症的成年人反射性血管舒张功能减弱，但他汀类药物治疗的成年人血管舒张功能没有减弱（∆Tor= 1.0°C时：正常= 36±1%CVCmax，高= 32±1%CVCmax，他汀类药物= 38±1%CVCmax;P <0.01）。∆SSNA并非不同(∆Tor = 1.0°C:正常:∆= 393±96%,高:∆= 311±120%,他汀类药物:∆= 256±90%;P = 0.11)。与正常胆固醇血症（0.09±0.02%CVCmax/%基线；P =0.024）和他汀类药物治疗（0.12±0.05%CVCmax/%基线；P =0.03）的成年人相比，高胆固醇血症的成年人（0.02±0.03%CVCmax/%基线）的SSNA:CVC关系斜率减弱。慢性他汀类药物治疗通过增加被动热应激时终端器官对交感神经流出的反应性，改善了前高胆固醇血症老年人的反射性皮肤血管扩张。
Key pointsImpairments in both central sympathetic and peripheral microvascular function contribute to blunted reflex cutaneous vasodilatation during heat stress in healthy older adults.Hypercholesterolaemia is associated with decrements in neurovascular function; however, little is known about the impact of hypercholesterolaemia on the integrated responses to heat stress. Further, whether chronic statin therapy alters skin sympathetic outflow or its relation to cutaneous vascular conductance during heat stress is unknown.We demonstrate that reflex cutaneous vasodilatation is impaired in older hypercholesterolaemic adults but not in formerly hypercholesterolaemic adults currently treated with a statin compared to age‐matched controls.Additionally, chronic statin treatment‐induced improvements in reflex vasodilatation are mediated, in part, by increases in end‐organ responsiveness to efferent sympathetic outflow during whole‐body heating.These data add to the growing body of literature substantiating the beneficial pleiotropic neurovascular effects of chronic statin treatment and provide further support for the use of statins to confer additional cardioprotective benefits in older adults.AbstractAttenuated reflex cutaneous vasodilatation in healthy human ageing is mediated by alterations in both central (sympathetic outflow) and peripheral (microvascular endothelial) function. Hypercholesterolaemia is associated with further impairments in neurovascular function. HMG‐CoA reductase inhibitors (statins) improve cutaneous endothelium‐dependent dilatation; however, whether statin therapy alters skin sympathetic nervous system activity (SSNA) or its relation to cutaneous vascular conductance (CVC) during passive heat stress is unknown. We hypothesized that (1) hypercholesterolaemic 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 vasodilatation in response to a 1.0°C rise in oral temperature (Tor; water perfused suit) was induced in 13 healthy normocholesterolaemic adults (62 ± 2 years; LDL = 113 ± 7 mg/dl), 10 hypercholesterolaemic adults (60 ± 1 years; LDL = 183 ± 2 mg/dl), and 10 previously hypercholesterolaemic adults (64 ± 1 years; LDL = 102 ± 2 mg/dl) treated with lipophilic statin (10–40 mg daily). SSNA (peroneal microneurography) and red cell flux (laser‐Doppler flowmetry) in the innervated dermatome (dorsum of foot) were continuously measured. Reflex vasodilatation was blunted in hypercholesterolaemic adults, but not in statin‐treated adults, compared to normocholesterolaemic adults (at ∆Tor= 1.0°C: normal = 36 ± 1%CVCmax, high = 32 ± 1%CVCmax, statin = 38 ± 1%CVCmax;P <0.01). ∆SSNA was not different (at ∆Tor= 1.0°C: normal: ∆ = 393 ± 96%, high: ∆ = 311 ± 120%, statin: ∆ = 256 ± 90%;P =0.11). The slope of the SSNA:CVC relation was blunted in hypercholesterolaemic adults (0.02 ± 0.03%CVCmax/%baseline) compared to both normocholesterolaemic (0.09 ± 0.02%CVCmax/%baseline;P =0.024) and statin‐treated (0.12 ± 0.05%CVCmax/%baseline;P =0.03) adults. Chronic statin treatment improves reflex cutaneous vasodilatation in formerly hypercholesterolaemic older adults by increasing end‐organ responsiveness to sympathetic outflow during passive heat stress.