Kvandal Per, Stefanovska Aneta, Veber Mitja, Kvernmo Hebe Désirée, Kirkebøen Knut Arvid
Department of Anesthesiology, Ulleval University Hospital, 0407 Oslo, Norway.
Microvasc Res. 2003 May;65(3):160-71. doi: 10.1016/s0026-2862(03)00006-2.
Nitric oxide (NO) and prostaglandines (PGs) are important in regulation of vascular tone and blood flow. Their contribution in human cutaneous circulation is still uncertain. We inhibited NO synthesis by infusing N(G)-monomethyl-L-arginine (L-NMMA) in the brachial artery (16 micromol/min for 5 min) and reversed it by intraarterial infusion of L-arginine (40 micromol/min for 7.5 min). PG synthesis was inhibited by the cyclooxygenase inhibitor aspirin (600 mg over 5 min intravenously). Basal cutaneous perfusion and perfusion responses during iontophoresis with the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) were recorded by laser Doppler flowmetry (LDF). We performed wavelet transforms of the measured signals. Mean spectral amplitude within the frequency interval from 0.0095 to 1.6 Hz and mean and normalized amplitudes of five intervals around 1, 0.3, 0.1, 0.04, and 0.01 Hz were analysed. The oscillations with frequencies around 1, 0.3, 0.1, and 0.04 Hz are influenced by the heartbeat, the respiration, the intrinsic myogenic activity of vascular smooth muscle, and the neurogenic activity of the vessel wall, respectively. We have previously shown that the oscillation with a frequency around 0.01 Hz is modulated by the vascular endothelium. L-NMMA reduced mean value of the LDF signal by approximately 20% (P = 0.0067). This reduction was reversed by L-arginine. Mean value of the LDF signals during ACh and SNP iontophoresis did not change after infusion of L-NMMA. Aspirin did not affect mean value of the LDF signal or the LDF signal during ACh or SNP iontophoresis. Before interventions the only significant difference between the effects of ACh and SNP was observed in the frequency around 0.01 Hz, where ACh increased normalized amplitude to a greater extent than SNP. L-NMMA abolished this difference, whereas it reappeared after infusion of L-arginine (P = 0.0084). Aspirin did not affect this difference (P = 0.006). We conclude that basal cutaneous blood flow and the endothelial dependency of the oscillation around 0.01 Hz are partly mediated by NO, but not by endogenous PGs. Other aspects of human cutaneous circulation studied are not regulated by NO or PGs.
一氧化氮(NO)和前列腺素(PGs)在调节血管张力和血流方面起着重要作用。它们在人体皮肤循环中的作用仍不明确。我们通过在肱动脉中输注N(G)-单甲基-L-精氨酸(L-NMMA,16微摩尔/分钟,持续5分钟)来抑制NO合成,并通过动脉内输注L-精氨酸(40微摩尔/分钟,持续7.5分钟)来逆转这种抑制。PG合成通过环氧化酶抑制剂阿司匹林(静脉内5分钟内给予600毫克)来抑制。使用激光多普勒血流仪(LDF)记录基础皮肤灌注以及在离子导入内皮依赖性血管舒张剂乙酰胆碱(ACh)和内皮非依赖性血管舒张剂硝普钠(SNP)期间的灌注反应。我们对测量信号进行了小波变换。分析了频率区间从0.0095至1.6赫兹内的平均频谱幅度以及围绕1、0.3、0.1、0.04和0.01赫兹的五个区间的平均幅度和归一化幅度。频率在1、0.3、0.1和0.04赫兹左右的振荡分别受心跳、呼吸、血管平滑肌的内在肌源性活动以及血管壁的神经源性活动影响。我们之前已经表明,频率在0.01赫兹左右的振荡受血管内皮调节。L-NMMA使LDF信号的平均值降低了约20%(P = 0.0067)。这种降低被L-精氨酸逆转。输注L-NMMA后,ACh和SNP离子导入期间LDF信号的平均值没有变化。阿司匹林不影响LDF信号的平均值或ACh或SNP离子导入期间的LDF信号。在干预前,ACh和SNP作用之间唯一显著的差异出现在0.01赫兹左右的频率处,其中ACh使归一化幅度增加的程度大于SNP。L-NMMA消除了这种差异,而在输注L-精氨酸后这种差异再次出现(P = 0.0084)。阿司匹林不影响这种差异(P = 0.006)。我们得出结论,基础皮肤血流以及0.01赫兹左右振荡的内皮依赖性部分由NO介导,但不由内源性PGs介导。所研究的人体皮肤循环的其他方面不受NO或PGs调节。