O'Donaughy T L, Walker B R
Vascular Physiology Group, Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131-5218, USA.
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2908-15. doi: 10.1152/ajpheart.2000.279.6.H2908.
Chronic hypoxia (CH) attenuates systemic vasoconstriction to a variety of agonists in conscious rats. Recent evidence suggests that similarly diminished responses to vasoconstrictors in aortic rings from CH rats may be due to increased endothelial heme oxygenase (HO) activity and enhanced production of the vasodilator carbon monoxide (CO). Thus we hypothesized that a hypoxia-induced increase in HO activity is responsible for decreased vasoconstrictor responsiveness observed in conscious CH rats. CH (4 wk at 0.5 atm) and control rats were renal denervated and instrumented for the measurement of renal blood flow (RBF) and blood pressure. First, renal vasoconstrictor responses to graded intravenous infusion of phenylephrine (PE) were assessed in conscious rats. CH rats demonstrated significantly diminished renal vasoconstrictor responses to PE compared with control responses that persisted even with acute restoration of normoxia. In additional experiments, CH rats exhibited increased renal vascular resistance and decreased RBF in response to the HO inhibitor zinc protoporphyrin IX (11 micromol/kg iv), whereas renal hemodynamics were unaffected by the inhibitor in control animals. Furthermore, we demonstrated greater HO enzyme activity in renal tissue from CH rats compared with controls. These data suggest that enhanced HO activity contributes a tonic vasodilatory influence in the renal vasculature of CH rats that may be responsible for the diminished sensitivity to vasoconstrictor agonists observed under these conditions.
慢性低氧（CH）会减弱清醒大鼠对多种激动剂的全身血管收缩反应。最近的证据表明，CH大鼠主动脉环对血管收缩剂的反应同样减弱，可能是由于内皮血红素加氧酶（HO）活性增加以及血管舒张剂一氧化碳（CO）生成增强所致。因此，我们推测低氧诱导的HO活性增加是导致清醒CH大鼠血管收缩反应性降低的原因。将CH（在0.5个大气压下持续4周）大鼠和对照大鼠进行肾去神经支配，并安装测量肾血流量（RBF）和血压的仪器。首先，在清醒大鼠中评估对分级静脉注射去氧肾上腺素（PE）的肾血管收缩反应。与对照反应相比，CH大鼠对PE的肾血管收缩反应明显减弱，即使急性恢复常氧后该反应仍持续存在。在另外的实验中，CH大鼠对HO抑制剂原卟啉锌IX（11微摩尔/千克静脉注射）表现出肾血管阻力增加和RBF降低，而在对照动物中该抑制剂对肾血流动力学没有影响。此外，我们证明CH大鼠肾组织中的HO酶活性高于对照。这些数据表明，HO活性增强对CH大鼠肾血管系统产生了一种持续性的血管舒张作用，这可能是导致在这些条件下观察到的对血管收缩激动剂敏感性降低的原因。
