Symons J D, Musch T I, Hageman K S, Stebbins C L
Department of Internal Medicine, University of California, Davis 95616, USA.
J Cardiovasc Pharmacol. 1999 Jul;34(1):116-23. doi: 10.1097/00005344-199907000-00019.
We hypothesized that nitric oxide (NO) opposes regional vasoconstriction caused by acute angiotensin II (ANG II) infusion in conscious rats. Mean arterial pressure (MAP), blood flow, and vascular conductance (regional blood flow/ MAP; ml/min/100 g/mm Hg) were measured and/or calculated before and at 2 min of ANG II infusion (0.05 or 1 microg/kg/min, i.a.) in the absence and presence of NO synthase (NOS) inhibition [N(G)-nitro-L-arginine methyl ester (L-NAME), 0.25 or 1 mg/kg, i.a.]. ANG II reduced stomach and hindlimb conductance only after NOS inhibition. For example, whereas 0.05 microg/kg/min ANG II did not attenuate conductance in the stomach (i.e., 1.04+/-0.08 to 0.93+/-0.12 ml/min/100 g/mm Hg), this variable was reduced (i.e., 0.57+/-0.14 to 0.34-/+0.05 ml/min/100 g/mm Hg; p < 0.05) when ANG II was infused after 0.25 mg/kg L-NAME. In addition, whereas hindlimb conductance was similar before and after administering 1 microg/kg/min ANG II (i.e., 0.13+/-0.01 and 0.09+/-0.02, respectively), this variable was reduced (i.e., 0.07+/-0.01 and 0.02+/-0.00, respectively; p < 0.05) when ANG II was infused after 1 mg/kg L-NAME. These findings indicate that NO opposes ANG II-induced vasoconstriction in the stomach and hindlimb. In contrast, whereas both doses of ANG II decreased (p < 0.05) vascular conductance in the kidneys and small and large intestine regardless of whether NOS inhibition was present, absolute vascular conductance was lower (p < 0.05) after L-NAME. For example, 1 microg/kg ANG II reduced renal conductance from 3.34+/-0.31 to 1.22+/-0.14 (p < 0.05). After 1 mg/kg L-NAME, renal conductance decreased from 1.39+/-0.18 to 0.72+/-0.16 (p < 0.05) during ANG II administration. Therefore the constrictor effects of NOS inhibition and ANG II are additive in these circulations. Taken together, our results indicate that the ability of NO to oppose ANG II-induced constriction is not homogeneous among regional circulations.
我们假设一氧化氮（NO）可对抗清醒大鼠急性输注血管紧张素II（ANG II）所引起的局部血管收缩。在不存在和存在一氧化氮合酶（NOS）抑制[左旋硝基精氨酸甲酯（L-NAME），0.25或1mg/kg，腹腔注射]的情况下，于输注ANG II（0.05或1μg/kg/min，腹腔注射）前及输注2分钟时测量和/或计算平均动脉压（MAP）、血流量和血管传导率（局部血流量/MAP；ml/min/100g/mm Hg）。仅在NOS抑制后，ANG II才降低胃和后肢的传导率。例如，0.05μg/kg/min的ANG II不会减弱胃的传导率（即从1.04±0.08降至0.93±0.12ml/min/100g/mm Hg），但在0.25mg/kg L-NAME后输注ANG II时，该变量降低（即从0.57±0.14降至0.34±0.05ml/min/100g/mm Hg；p<0.05）。此外，在给予1μg/kg/min ANG II前后后肢传导率相似（分别为0.13±0.01和0.09±0.02），但在1mg/kg L-NAME后输注ANG II时，该变量降低（分别为0.07±0.01和0.02±0.00；p<0.05）。这些发现表明，NO可对抗ANG II诱导的胃和后肢血管收缩。相比之下，无论是否存在NOS抑制，两种剂量的ANG II均降低（p<0.05）肾脏以及小肠和大肠的血管传导率，但L-NAME后绝对血管传导率更低（p<0.05）。例如，1μg/kg ANG II使肾传导率从3.34±0.31降至1.22±0.14（p<0.05）。在1mg/kg L-NAME后，ANG II给药期间肾传导率从1.39±0.18降至0.72±0.16（p<0.05）。因此，在这些循环中，NOS抑制和ANG II的收缩作用是相加的。综上所述，我们的结果表明，NO对抗ANG II诱导的收缩的能力在局部循环中并非均匀一致。
