Yoshimura T, Arita M, Kobayashi M
Department of Physiology, Faculty of Medicine, Medical College of Oita, Japan.
Jpn J Physiol. 1988;38(4):459-78. doi: 10.2170/jjphysiol.38.459.
We studied contractile properties of portal veins isolated from chronic portal hypertensive rats (PHR) resulting from liver cirrhosis, a model obtained by repeated subcutaneous injections of CCl4 (2 mg/kg) twice weekly for over 45 weeks. Portal venous pressure in vivo was significantly higher in PHR (167.0 +/- 38.7 mmH2O) than in the control normal Wistar rats (NWR) (102.0 +/- 25.5 mmH2O). A pair of portal veins from PHR and NWR were mounted longitudinally in an organ bath and perfused with Tyrode's solution with different K+, Ca2+, and norepinephrine concentrations. The isometric tension was measured by a strain-gauge. Under control conditions, spontaneous phasic contractile force, corrected by cross-sectional area, was greater, and the frequency was lower in PHR than in NWR preparations. The averaged peak contractile force measured at different [K]o (5.4-86.4 mM) was also greater in PHR than in NWR. Force of the tonic contraction measured at different [Ca]o (0.45-5.4 mM), under conditions of 86.4 mM [K]o was significantly larger in PHR than in NWR preparations. However, the Ca2+ sensitivity of both preparations was the same. D-600 (greater than or equal to 0.1 microM) inhibited the tonic contraction in both preparations with an identical sensitivity to the drug. In the presence of norepinephrine (10 microM), the Ca2+ sensitivity of the tonic contraction increased both in PHR and NWR preparations. The increase was more pronounced in PHR and was completely reversed in the presence of the alpha 1-adrenoceptor blocker, prazosin (0.1 microM). The alpha 1-adrenoceptor sensitivity to norepinephrine was not altered in PHR preparations. The rate of Ca2+ release and uptake of intracellular Ca2+ seemed identical in both preparations. Thus, in the absence of norepinephrine, the phasic and tonic contractile forces of portal veins from PHR are larger than that of NWR, probably due to increased membrane Ca2+ permeability. The PHR preparations have a higher affinity for external Ca2+ in the presence of norepinephrine, an additional factor contributing to elevation of portal blood pressure in the presence of chronic liver cirrhosis.
我们研究了从肝硬化所致慢性门静脉高压大鼠（PHR）分离出的门静脉的收缩特性，该模型通过每周两次皮下注射四氯化碳（2mg/kg）持续超过45周获得。PHR大鼠的体内门静脉压力（167.0±38.7 mmHg₂O）显著高于对照正常Wistar大鼠（NWR）（102.0±25.5 mmHg₂O）。将一对来自PHR和NWR的门静脉纵向安装在器官浴槽中，并用含有不同钾离子、钙离子和去甲肾上腺素浓度的台氏液灌注。通过应变片测量等长张力。在对照条件下，经横截面积校正后的自发性阶段性收缩力在PHR中比在NWR制剂中更大，且频率更低。在不同的[K]o（5.4 - 86.4 mM）下测量的平均峰值收缩力在PHR中也比在NWR中更大。在86.4 mM [K]o条件下，在不同的[Ca]o（0.45 - 5.4 mM）下测量的强直性收缩力在PHR中比在NWR制剂中显著更大。然而，两种制剂的钙离子敏感性相同。D - 600（≥0.1 μM）以相同的药物敏感性抑制两种制剂的强直性收缩。在存在去甲肾上腺素（10 μM）的情况下，PHR和NWR制剂中强直性收缩的钙离子敏感性均增加。这种增加在PHR中更明显，并且在存在α₁ - 肾上腺素能受体阻滞剂哌唑嗪（0.1 μM）时完全逆转。PHR制剂中对去甲肾上腺素的α₁ - 肾上腺素能受体敏感性未改变。两种制剂中钙离子的释放速率和细胞内钙离子的摄取似乎相同。因此，在不存在去甲肾上腺素的情况下，PHR门静脉的阶段性和强直性收缩力比NWR的更大，这可能是由于膜钙离子通透性增加所致。在存在去甲肾上腺素的情况下，PHR制剂对细胞外钙离子具有更高的亲和力，这是导致慢性肝硬化时门静脉血压升高的另一个因素。
