Newton Christopher R, Curran Brian, Victorino Gregory P
Department of Surgery, University of California at San Francisco-East Bay, Alameda County Medical Center, Oakland, CA 94602, USA.
Surgery. 2004 Nov;136(5):1054-60. doi: 10.1016/j.surg.2004.04.031.
In addition to its vasoconstricting effects, angiotensin II (Ang II) has also demonstrated the ability to modulate microvessel permeability. We hypothesized that activation of the angiotensin II type 1 receptor (AT1) would increase hydraulic permeability.
Hydraulic permeability (L(p)) was measured in rat mesenteric venules using the Landis micro-occlusion technique. Paired measures of L(p) were obtained at baseline and after perfusion with the AT1 agonist, [Sar(1)]-angiotensin II, at 10 micromol/L (n=6) and 100 micromol/L (n=6). Activation of the AT1 receptor was also achieved by perfusion with 20 nmol/L Ang II plus the angiotensin II type 2 receptor (AT2) antagonist, PD123319. In these studies, 30 micromol/L (n=6) and 300 micromol/L (n=6) of PD123319 were used.
[Sar(1)]-angiotensin II increased L(p) 2-fold with the 10 micromol/L dose (P=.04) and 4-fold with the 100 micromol/L dose (P < .001). The L(p) peak due to [Sar(1)]-angiotensin II occurred sooner than the peak observed with Ang II. PD123319 (30 micromol/L) plus 20 nmol/L Ang II increased L(p) 5-fold (P=.003), while PD123319 (300 micromol/L) plus 20 nmol/L Ang II increased L(p) 20-fold (P < .0001). The magnitude of the effect due to PD123319 (300 micromol/L) plus Ang II (20 nmol/L) was approximately twice the summation of effects due to PD123319 (300 micromol/L) alone and Ang II (20 nmol/L) alone.
We conclude that endothelial cell Ang II receptors play an important role in modulating transendothelial fluid flux. Activating the AT1 receptor increases L(p); the AT2 receptor may operate to oppose this action. Pharmacologic manipulation of Ang II receptors may be beneficial during shock states to limit intravascular fluid loss.
除血管收缩作用外，血管紧张素II（Ang II）还具有调节微血管通透性的能力。我们推测，血管紧张素II 1型受体（AT1）的激活会增加水通透性。
采用兰迪斯微阻塞技术测量大鼠肠系膜静脉的水通透性（L(p)）。在基线以及用10微摩尔/升（n = 6）和100微摩尔/升（n = 6）的AT1激动剂[Sar(1)]-血管紧张素II灌注后，获取L(p)的配对测量值。通过用20纳摩尔/升Ang II加血管紧张素II 2型受体（AT2）拮抗剂PD123319灌注也可实现AT1受体的激活。在这些研究中，使用了30微摩尔/升（n = 6）和300微摩尔/升（n = 6）的PD123319。
[Sar(1)]-血管紧张素II在10微摩尔/升剂量时使L(p)增加2倍（P = 0.04），在100微摩尔/升剂量时使L(p)增加4倍（P < 0.001）。[Sar(1)]-血管紧张素II引起的L(p)峰值出现得比Ang II观察到的峰值更早。PD123319（30微摩尔/升）加20纳摩尔/升Ang II使L(p)增加5倍（P = 0.003），而PD123319（300微摩尔/升）加20纳摩尔/升Ang II使L(p)增加20倍（P < 0.0001）。PD123319（300微摩尔/升）加Ang II（20纳摩尔/升）产生的效应大小约为单独使用PD123319（300微摩尔/升）和单独使用Ang II（20纳摩尔/升）产生的效应总和的两倍。
我们得出结论，内皮细胞Ang II受体在调节跨内皮液体通量中起重要作用。激活AT1受体可增加L(p)；AT2受体可能起相反作用。在休克状态下，对Ang II受体进行药物干预可能有助于限制血管内液体流失。
