Fitzgerald Sharyn M, Bashari Homaira, Cox Jessica A, Parkington Helena C, Evans Roger G
Department of Physiology, Monash University, Melbourne, Victoria 3800, Australia.
Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H1072-82. doi: 10.1152/ajpheart.00072.2007. Epub 2007 Apr 27.
We determined the contributions of various endothelium-derived relaxing factors to control of basal vascular tone and endothelium-dependent vasodilation in the mouse hindlimb in vivo. Under anesthesia, catheters were placed in a carotid artery, jugular vein, and femoral artery (for local hindlimb circulation injections). Hindlimb blood flow (HBF) was measured by transit-time ultrasound flowmetry. N(omega)-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg plus 10 mg x kg(-1) x h(-1)), to block nitric oxide (NO) production, altered basal hemodynamics, increasing mean arterial pressure (30 +/- 3%) and reducing HBF (-30 +/- 12%). Basal hemodynamics were not significantly altered by indomethacin (10 mg x kg(-1) x h(-1)), charybdotoxin (ChTx, 3 x 10(-8) mol/l), apamin (2.5 x 10(-7) mol/l), or ChTx plus apamin (to block endothelium-derived hyperpolarizing factor; EDHF). Hyperemic responses to local injection of acetylcholine (2.4 microg/kg) were reproducible in vehicle-treated mice and were not significantly attenuated by L-NAME alone, indomethacin alone, L-NAME plus indomethacin with or without co-infusion of diethlyamine NONOate to restore resting NO levels, ChTx alone, or apamin alone. Hyperemic responses evoked by acetylcholine were reduced by 29 +/- 11% after combined treatment with apamin plus charybdotoxin, and the remainder was virtually abolished by additional treatment with L-NAME but not indomethacin. None of the treatments altered the hyperemic response to sodium nitroprusside (5 microg/kg). We conclude that endothelium-dependent vasodilation in the mouse hindlimb in vivo is mediated by both NO and EDHF. EDHF can fully compensate for the loss of NO, but this cannot be explained by tonic inhibition of EDHF by NO. Control of basal vasodilator tone in the mouse hindlimb is dominated by NO.
我们测定了多种内皮源性舒张因子对小鼠后肢体内基础血管张力及内皮依赖性血管舒张的调控作用。在麻醉状态下，将导管分别置于颈动脉、颈静脉及股动脉（用于后肢局部循环注射）。采用渡越时间超声血流仪测量后肢血流量（HBF）。通过N（ω）-硝基-L-精氨酸甲酯（L-NAME，50 mg/kg加10 mg·kg⁻¹·h⁻¹）阻断一氧化氮（NO）生成，可改变基础血流动力学，使平均动脉压升高（30±3%），HBF降低（-30±12%）。吲哚美辛（10 mg·kg⁻¹·h⁻¹）、蝎毒素（ChTx，3×10⁻⁸ mol/L）、蜂毒明肽（2.5×10⁻⁷ mol/L）或ChTx加蜂毒明肽（用于阻断内皮源性超极化因子；EDHF）对基础血流动力学无显著影响。在给予溶媒处理的小鼠中，局部注射乙酰胆碱（2.4 μg/kg）所引发的充血反应具有重复性，单独使用L-NAME、单独使用吲哚美辛、L-NAME加吲哚美辛（无论是否同时输注二乙胺NONOate以恢复静息NO水平）、单独使用ChTx或单独使用蜂毒明肽均未使其显著减弱。联合使用蜂毒明肽和蝎毒素后，乙酰胆碱引发的充血反应降低了29±11%，进一步用L-NAME而非吲哚美辛处理后，其余反应几乎完全消失。所有处理均未改变对硝普钠（5 μg/kg）的充血反应。我们得出结论，小鼠后肢体内的内皮依赖性血管舒张由NO和EDHF共同介导。EDHF可完全代偿NO的缺失，但这无法用NO对EDHF的紧张性抑制来解释。小鼠后肢基础血管舒张张力的调控主要由NO主导。
