Kellogg Dean L, Zhao Joan L, Wu Yubo
Division of Geriatrics and Gerontology, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229, USA.
J Physiol. 2008 Feb 1;586(3):847-57. doi: 10.1113/jphysiol.2007.144642. Epub 2007 Nov 29.
The physiological roles of constitutively expressed nitric oxide synthase (NOS) isoforms in humans, in vivo, are unknown. Cutaneous vasodilatation during both central nervous system-mediated, thermoregulatory reflex responses to whole-body heat stress and during peripheral axon reflex-mediated, local responses to skin warming in humans depend on nitric oxide (NO) generation by constitutively expressed NOS of uncertain isoform. We hypothesized that neuronal NOS (nNOS, NOS I) effects cutaneous vasodilatation during whole-body heat stress, but not during local skin warming. We examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) administered by intradermal microdialysis on vasodilatation induced by whole-body heat stress or local skin warming. Skin blood flow (SkBF) was monitored by laser-Doppler flowmetry (LDF). Blood pressure (MAP) was monitored and cutaneous vascular conductance calculated (CVC = LDF/MAP). In protocol 1, whole-body heat stress was induced with water-perfused suits. In protocol 2, local skin warming was induced through local warming units at LDF sites. At the end of each protocol, 56 mm sodium nitroprusside was perfused at microdialysis sites to raise SkBF to maximal levels for data normalization. 7-NI significantly attenuated CVC increases during whole-body heat stress (P < 0.05), but had no effect on CVC increases induced by local skin warming (P > 0.05). These diametrically opposite effects of 7-NI on two NO-dependent processes verify selective nNOS antagonism, thus proving that the nNOS isoform affects NO increases and hence vasodilatation during centrally mediated, reflex responses to whole-body heat stress, but not during locally mediated, axon reflex responses to local skin warming. We conclude that the constitutively expressed nNOS isoform has distinct physiological roles in cardiovascular control mechanisms in humans, in vivo.
在人体中，组成型表达的一氧化氮合酶（NOS）亚型的生理作用尚不清楚。在中枢神经系统介导的对全身热应激的体温调节反射反应过程中，以及在周围轴突反射介导的对人体皮肤升温的局部反应过程中，皮肤血管舒张均依赖于由不确定亚型的组成型表达的NOS产生的一氧化氮（NO）。我们假设神经元型NOS（nNOS，NOS I）在全身热应激期间影响皮肤血管舒张，但在局部皮肤升温期间不影响。我们研究了通过皮内微透析给予nNOS抑制剂7-硝基吲唑（7-NI）对全身热应激或局部皮肤升温诱导的血管舒张的影响。通过激光多普勒血流仪（LDF）监测皮肤血流量（SkBF）。监测血压（MAP）并计算皮肤血管传导率（CVC = LDF/MAP）。在方案1中，用水灌注服诱导全身热应激。在方案2中，通过LDF部位的局部加热装置诱导局部皮肤升温。在每个方案结束时，在微透析部位灌注56毫米硝普钠，以使SkBF升高至最大水平以进行数据标准化。7-NI显著减弱了全身热应激期间CVC的增加（P < 0.05），但对局部皮肤升温诱导的CVC增加没有影响（P > 0.05）。7-NI对两个NO依赖性过程的这些截然相反的作用证实了选择性nNOS拮抗作用，从而证明nNOS亚型在中枢介导的对全身热应激的反射反应期间影响NO增加并因此影响血管舒张，但在局部介导的对局部皮肤升温的轴突反射反应期间不影响。我们得出结论，组成型表达的nNOS亚型在人体心血管控制机制中具有不同的生理作用。
