Hartleb M, Moreau R, Gaudin C, Lebrec D
Laboratoire d'Hémodynamique Splanchnique, INSERUM U-24, Hôpital Beaujon, Clichy, France.
J Hepatol. 1995 Feb;22(2):202-7. doi: 10.1016/0168-8278(95)80430-7.
BACKGROUND/AIMS: In cirrhosis, the mechanism(s) for vascular hyporesponsiveness to vasoconstrictors such as, alpha 1-adrenoceptor agonists, vasopressin and angiotensin II, are unclear. Moreover, vascular reactivity to substances such as L-type calcium channel activators is unknown.
Thus, pressor dose-response curves to vasoconstrictors [phenylephrine (an alpha 1-agonist, 0.1-500 micrograms/kg) angiotensin II (10-500 ng/kg), vasopressin (0.01-5 IU/kg), and Bay K 8644 (an L-type calcium channel activator, 0.5-50 micrograms/kg)] were obtained in normal rats and in rats with secondary biliary cirrhosis. All experiments were performed in ganglionic-blocked animals to limit the influence of cardiovascular reflexes. Doses of vasoconstrictor necessary to obtain a 40 mmHg increase in arterial pressure (D40) were calculated.
Compared to normal animals, rats with cirrhosis had significantly higher D40 values for angiotensin II (171 +/- 57 vs. 344 +/- 41 ng/kg), phenylephrine (2.6 +/- 0.2 vs. 26.4 +/- 10.7 micrograms/kg) and vasopressin (73 +/- 19 vs. 401 +/- 150 mU/kg). Pressor responses to Bay K 8644 did not differ between normal rats and rats with cirrhosis (8.8 +/- 0.9 vs. 10.5 +/- 2.1 micrograms/kg).
In conclusion, this study shows that cirrhosis produces vascular hyporeactivity to phenylephrine, vasopressin and angiotensin II but not to Bay K 8644. Therefore, cirrhosis impairs certain constrictor mechanisms which are shared by phenylephrine, angiotensin II and vasopressin but which do not contribute to the vascular response to Bay K 8644.
背景/目的：在肝硬化中，血管对血管收缩剂（如α1 - 肾上腺素受体激动剂、血管加压素和血管紧张素II）反应性降低的机制尚不清楚。此外，血管对诸如L型钙通道激活剂等物质的反应性也未知。
因此，在正常大鼠和继发性胆汁性肝硬化大鼠中获得了对血管收缩剂[去氧肾上腺素（一种α1 - 激动剂，0.1 - 500微克/千克）、血管紧张素II（10 - 500纳克/千克）、血管加压素（0.01 - 5国际单位/千克）和Bay K 8644（一种L型钙通道激活剂，0.5 - 50微克/千克）]的升压剂量 - 反应曲线。所有实验均在神经节阻断的动物中进行，以限制心血管反射的影响。计算使动脉压升高40 mmHg所需的血管收缩剂剂量（D40）。
与正常动物相比，肝硬化大鼠对血管紧张素II（171±57对344±41纳克/千克）、去氧肾上腺素（2.6±0.2对26.4±10.7微克/千克）和血管加压素（73±19对401±150毫单位/千克）的D40值显著更高。正常大鼠和肝硬化大鼠对Bay K 8644的升压反应无差异（8.8±0.9对10.5±2.1微克/千克）。
总之，本研究表明肝硬化会导致血管对去氧肾上腺素、血管加压素和血管紧张素II反应性降低，但对Bay K 8644无此影响。因此，肝硬化损害了去氧肾上腺素、血管紧张素II和血管加压素共有的某些收缩机制，但这些机制对血管对Bay K 8644的反应无作用。
