Schmetterer L, Findl O, Strenn K, Graselli U, Kastner J, Eichler H G, Wolzt M
Department of Clinical Pharmacology, Vienna University, Austria.
Am J Physiol. 1997 Dec;273(6):R2005-12. doi: 10.1152/ajpregu.1997.273.6.R2005.
It is well known that changes in PCO2 or PO2 strongly influence cerebral and ocular blood flow. However, the mediators of these changes have not yet been completely identified. There is evidence from animal studies that NO may play a role in hypercapnia-induced vasodilation and that NO synthase inhibition modulates the response to hyperoxia in the choroid. Hence we have studied the effect of NO synthase inhibition by NG-monomethyl-L-arginine (L-NMMA, 3 mg/kg over 5 min as a bolus followed by a continuous infusion of 30 micrograms.kg-1.min-1) on the changes of cerebral and ocular hemodynamic parameters elicited by hypercapnia and hyperoxia in healthy young subjects. Mean flow velocities in the middle cerebral artery and the ophthalmic artery were measured with Doppler ultrasound, and ocular fundus pulsation amplitude, which estimates pulsatile choroidal blood flow, was measured with laser interferometry Administration of L-NMMA reduced ocular fundus pulsation. (-19%, P < 0.005) but only slightly reduced mean flow velocities in the larger arteries. Hypercapnia (PCO2 = 48 mmHg) significantly increased mean flow velocities in the middle cerebral artery (+26%, P < 0.01) and fundus pulsation amplitude (+16%, P < 0.005) but did not change mean flow velocity in the ophthalmic artery. The response to hypercapnia in the middle cerebral artery (P < 0.05) and in the choroid (P < 0.05) was significantly blunted by L-NMMA. On the contrary, L-NMMA did not affect hyperoxia-induced (PO2 = 530 mmHg) hemodynamic changes. The hemodynamic effects of L-NMMA (at baseline and during hypercapnia) were reversed by coadministration of L-arginine. The present study supports the concept that NO has a role in hypercapnia induced vasodilation in humans.
众所周知，PCO₂或PO₂的变化会强烈影响脑血流量和眼血流量。然而，这些变化的介质尚未完全明确。动物研究表明，NO可能在高碳酸血症诱导的血管舒张中起作用，并且一氧化氮合酶抑制可调节脉络膜对高氧的反应。因此，我们研究了NG-单甲基-L-精氨酸（L-NMMA，3mg/kg，静脉推注5分钟，随后以30μg·kg⁻¹·min⁻¹持续输注）抑制一氧化氮合酶对健康年轻受试者高碳酸血症和高氧引起的脑和眼血流动力学参数变化的影响。用多普勒超声测量大脑中动脉和眼动脉的平均流速，并用激光干涉测量法测量估计脉络膜搏动性血流的眼底搏动幅度。给予L-NMMA可降低眼底搏动（-19%，P<0.005），但仅轻微降低较大动脉的平均流速。高碳酸血症（PCO₂=48mmHg）显著增加大脑中动脉的平均流速（+26%，P<0.01）和眼底搏动幅度（+16%，P<0.005），但不改变眼动脉的平均流速。L-NMMA显著减弱了大脑中动脉（P<0.05）和脉络膜（P<0.05）对高碳酸血症的反应。相反，L-NMMA不影响高氧（PO₂=530mmHg）引起的血流动力学变化。同时给予L-精氨酸可逆转L-NMMA（基线和高碳酸血症期间）的血流动力学效应。本研究支持NO在人类高碳酸血症诱导的血管舒张中起作用这一观点。
