Vasopressin reverses mesenteric hyperemia and vasoconstrictor hyporesponsiveness in anesthetized portal hypertensive rats
Vasopressin reverses mesenteric hyperemia and vasoconstrictor hyporesponsiveness in anesthetized portal hypertensive rats
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DOI：
10.1002/hep.510280307
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发表时间：
1998-09-01
期刊：
影响因子：
13.5
通讯作者：
Stauber, RE
中科院分区：
文献类型：
--
作者：
Heinemann, A;Wachter, CH;Stauber, RE
我们最近报道了血管加压素类似物纠正门脉高压大鼠体外血管对肾上腺素能血管收缩药的低反应性。为探讨加压素在体内能否通过恢复血管收缩反应减少门静脉结扎(PVL)大鼠的内脏血流量，采用超声传递时移技术进行血流量测定。在基础状态下，PVL大鼠肠系膜上动脉的血流量是假手术对照组大鼠的1.6倍。PVL大鼠对肾上腺素受体激动剂苯肾上腺素(0.03~1mU·min~(-1)·kg~(-1))、特利加压素(2~20mU·g·kg~(-1))和精氨酸加压素(3~300mU·min~(-1)·kg~(-1))也表现出钝化的肠系膜收缩反应，并呈剂量依赖性减少，在最高剂量时甚至消失。当表现为相对于基线的百分比变化时，与假手术大鼠相比，PVL大鼠的肠系膜动脉对特利加压素和精氨酸加压素的反应增强。此外，特利加压素(20 mU·kg~(-1))可逆转PVL大鼠肠系膜对苯肾上腺素的低反应性。这些加压素效应不依赖于一氧化氮(NO)途径，因为它们不能被N(G)-硝基-L-精氨酸甲酯(L-NAME)(0.1-10 mg·kg(-1))抑制NO合成所模拟。这些数据表明，药理剂量的加压素通过恢复门脉高压大鼠对肾上腺素能血管收缩药的反应性来逆转内脏充血。
We recently reported that vasopressin analogues correct the in vitro vascular hyporeactivity to adrenergic vasoconstrictors in portal hypertensive rats. The aim of the present study was to determine whether vasopressin reduces splanchnic blood flow in portal vein-ligated (PVL) rats by restoring vasoconstrictor responsiveness in vivo, The ultrasonic transit time-shift technique was used for blood flow measurements. At basal conditions, blood flow through the superior mesenteric artery was elevated 1.6-fold in PVL rats as compared with sham-operated (SHAM) control rats. PVL rats also exhibited blunted mesenteric constrictor responses to the adrenoceptor agonist, phenylephrine (0.03-1 mu mol.min(-1).kg(-1)), Terlipressin (2-20 mu g.kg(-1)) and arginine vasopressin (3-300 mu mol.min(-1).kg(-1)) dose-dependently reduced, and at the highest doses, even abolished, the difference in mesenteric blood flow (MBF) between PVL and SHAM rats. When expressed as percent changes relative to baseline, mesenteric arterial responses to terlipressin and arginine vasopressin were found to be enhanced in PVL rats as compared with SHAM rats. Moreover, pretreatment with terlipressin (20 mu g.kg(-1)) reversed the mesenteric hyporesponsiveness to phenylephrine of PVL rats. These vasopressin effects were independent of the nitric oxide (NO) pathway, because they were not mimicked by inhibition of NO synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME) (0.1-10 mg.kg(-1)). These data indicate that pharmacological doses of vasopressin reverse the splanchnic hyperemia by restoring the responsiveness to adrenergic vasoconstrictors in portal hypertensive rats.