Thomas S H, Joh T, Benoit J N
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130-3932.
Dig Dis Sci. 1991 Sep;36(9):1243-8. doi: 10.1007/BF01307516.
Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia.
我们实验室之前的研究表明，体液因子，即胰高血糖素，可导致肝前性门静脉高压大鼠约30%的内脏血管舒张。血管对去甲肾上腺素、血管加压素和血管紧张素II的敏感性降低可能导致内脏血管舒张。然而，无论是胰高血糖素还是血管收缩剂敏感性的改变都不能完全解释门静脉高压患者中观察到的内脏血管舒张。因此，本研究旨在探讨胆汁酸在门静脉高压内脏充血中的作用，因为（1）门静脉高压患者血清胆汁酸升高，（2）胆汁酸是强力的肠道血管舒张剂。通过手术结扎门静脉在Sprague-Dawley大鼠中诱导肝前性门静脉高压。门静脉高压诱导10至14天后，通过手术中断对照大鼠和门静脉高压大鼠的肠肝循环。将动物置于Bollman束缚笼中并使其恢复。18至24小时后，用戊巴比妥钠麻醉大鼠，并用放射性微球测量局部血流。无胆瘘的正常大鼠和门静脉高压大鼠作为对照。通过放射免疫测定法测量的门静脉高压动物的血浆胆汁酸水平比对照动物高约3.8倍。胆管插管有效地耗尽了正常大鼠和门静脉高压大鼠的循环胆汁酸池，并显著降低了门静脉高压大鼠而非对照大鼠的门静脉流入量。由于胆汁酸耗竭并未完全消除胃肠道充血，提示胆汁酸作为门静脉高压内脏充血的部分介质发挥作用。
