补充L-精氨酸或抑制精氨酸酶可增强老年人皮肤的反射性皮肤血管舒张。
L-Arginine supplementation or arginase inhibition augments reflex cutaneous vasodilatation in aged human skin.
作者信息
Holowatz Lacy A, Thompson Caitlin S, Kenney W Larry
机构信息
Department of Kinesiology, Noll Laboratory, Pennsylvania State University, University Park, PA 16802, USA.
出版信息
J Physiol. 2006 Jul 15;574(Pt 2):573-81. doi: 10.1113/jphysiol.2006.108993. Epub 2006 May 4.
Full expression of reflex cutaneous vasodilatation is dependent on nitric oxide (NO) and vasodilatation is attenuated in healthy older humans. NO bioavailability in aged skin may be decreased by an age-related upregulation of arginase, which reciprocally regulates the NO-synthase (NOS) substrate L-arginine (L-Arg). We hypothesized that increased arginase activity contributes to attenuated vasodilatation in aged skin by limiting L-Arg for NOS-mediated NO synthesis. Five microdialysis fibres were placed in forearm skin of 10 young (Y, 23 +/- 1 years) and 9 older (O, 68 +/- 1 years) human subjects, serving as control (C, Ringer solution), NOS-inhibited (10.0 mM NG-nitro-L-arginine), arginase-inhibited (5.0 mM (S)-(2-boronoethyl)-L-cysteine + 5.0 mM Nomega-hydroxy-nor-L-arginine), L-arg supplemented (L-Arg; 10.0 mM L-arginine) and combined arginase-inhibited + L-Arg sites. After 20 min thermoneutral baseline, cutaneous vasodilatation was induced by passive whole-body heating to increase oral temperature (Tor) by 1.0 degrees C. Red blood cell flux was measured by laser-Doppler flowmetry over each microdialysis site. Cutaneous vascular conductance was calculated (CVC = flux/mean arterial pressure) and normalized to maximal CVC (CVCmax, 28.0 mM sodium nitroprusside + local heating to 43 degrees C). Cutaneous vasodilatation during heating was attenuated in O (Y, 42 +/- 1, versus O, 30 +/- 1%CVCmax, P < 0.001) at control sites. NOS inhibition decreased vasodilatation in both age groups compared to C (Y, 22 +/- 2; O, 18 +/- 2%CVCmax; P < 0.001). Arginase inhibition, L-Arg supplementation, and arginase inhibition + L-Arg supplementation augmented vasodilatation in O (arginase-inhibited, 46 +/- 4; L-Arg, 44 +/- 4; arginase-inhibited + L-arg, 46 +/- 5%CVCmax; P < 0.001 versus C) but not in Y (arginase-inhibited, 46 +/- 4; L-Arg, 38 +/- 4; arginase-inhibited + L-Arg, 44 +/- 4%CVCmax; P > 0.05 versus C). Increasing L-Arg for NO synthesis by either arginase inhibition or direct L-Arg supplementation restores the age-related deficit in reflex cutaneous vasodilatation.
反射性皮肤血管舒张的充分表达依赖于一氧化氮（NO），而在健康的老年人中血管舒张作用减弱。老年皮肤中NO的生物利用度可能因精氨酸酶随年龄增长而上调而降低，精氨酸酶可反向调节NO合酶（NOS）的底物L-精氨酸（L-Arg）。我们推测，精氨酸酶活性增加通过限制用于NOS介导的NO合成的L-Arg，导致老年皮肤血管舒张减弱。将五根微透析纤维置于10名年轻（Y，23±1岁）和9名老年（O，68±1岁）人体受试者的前臂皮肤中，分别作为对照（C，林格溶液）、NOS抑制组（10.0 mM NG-硝基-L-精氨酸）、精氨酸酶抑制组（5.0 mM （S）-（2-硼乙基）-L-半胱氨酸 + 5.0 mM Nω-羟基-L-精氨酸）、L-Arg补充组（L-Arg；10.0 mM L-精氨酸）以及精氨酸酶抑制 + L-Arg联合组。在20分钟的热中性基线期后，通过被动全身加热诱导皮肤血管舒张，使口腔温度（Tor）升高1.0℃。通过激光多普勒血流仪在每个微透析部位测量红细胞通量。计算皮肤血管传导率（CVC = 通量/平均动脉压），并将其归一化为最大CVC（CVCmax，28.0 mM硝普钠 + 局部加热至43℃）。在对照部位，加热期间老年组（Y组，42±1，O组，30±1%CVCmax，P < 0.001）的皮肤血管舒张减弱。与C组相比，NOS抑制使两个年龄组的血管舒张均降低（Y组，22±2；O组，18±2%CVCmax；P < 0.001）。精氨酸酶抑制、L-Arg补充以及精氨酸酶抑制 + L-Arg补充可增强老年组的血管舒张（精氨酸酶抑制组，46±4；L-Arg组，44±4；精氨酸酶抑制 + L-Arg组，46±5%CVCmax；与C组相比P < 0.001），但在年轻组中无此作用（精氨酸酶抑制组，46±4；L-Arg组，38±4；精氨酸酶抑制 + L-Arg组，44±4%CVCmax；与C组相比P > 0.05）。通过精氨酸酶抑制或直接补充L-Arg增加用于NO合成的L-Arg，可恢复与年龄相关的反射性皮肤血管舒张缺陷。
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