Huang Y T, Lin H C, Tsai J F, Hou M C, Lee S D, Hong C Y
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
J Hepatol. 1998 Jun;28(6):1037-44. doi: 10.1016/s0168-8278(98)80354-1.
BACKGROUND/AIMS: Portal hypertension is associated with decreased vascular responsiveness to vasoconstrictors, which may contribute to the hyperdynamics. Isosorbide dinitrate is an effective portal hypotensive drug. The present study aimed to investigate whether chronic administration of isosorbide dinitrate could affect vascular responsiveness in portal hypertensive rats.
Portal hypertension was induced by partial portal vein ligation. Sham-operated (Sham) rats served as controls. There were four animal groups for this study: portal vein ligation-isosorbide dinitrate group, portal vein ligation-vehicle (Veh) group, Sham-isosorbide dinitrate group and Sham-Veh group. Isosorbide dinitrate (5 mg x kg(-1) x 12 h(-1) was given by gavage for 8 days starting 1 day before ligation and continuing thereafter. Mesenteric arteries were removed for contractile study after hemodynamic measurement.
Contractile responses to KCI (15-90 mM) and phenylephrine (10(-9)-10(-4) M) were recorded. Both vascular reactivity and sensitivity were significantly reduced in portal vein ligation rats as compared to Sham rats. Chronic isosorbide dinitrate treatment reduced portal venous pressure in portal vein ligation rats. Moreover, the maximal contractile responses to KCl and phenylephrine were significantly enhanced in both portal vein ligation and Sham rats after isosorbide dinitrate treatment, but relative hyporeactivity persisted in portal vein ligation rats. In contrast, a single dose of isosorbide dinitrate did not alter the contractile sensitivity or reactivity to KCl or phenylephrine in either portal vein ligation or Sham rats.
Our results show that long-term administration of isosorbide dinitrate enhanced vascular contractility in both portal vein ligation and Sham rats, but relative hyporeactivity persisted in portal vein ligation rats.
背景/目的：门静脉高压与血管对血管收缩剂的反应性降低有关，这可能导致高动力循环。硝酸异山梨酯是一种有效的门静脉降压药物。本研究旨在探讨长期给予硝酸异山梨酯是否会影响门静脉高压大鼠的血管反应性。
通过部分门静脉结扎诱导门静脉高压。假手术（Sham）大鼠作为对照。本研究有四个动物组：门静脉结扎-硝酸异山梨酯组、门静脉结扎-溶剂（Veh）组、Sham-硝酸异山梨酯组和Sham-Veh组。从结扎前1天开始，持续8天，每天经口灌胃给予硝酸异山梨酯（5 mg·kg⁻¹·12 h⁻¹）。血流动力学测量后，取出肠系膜动脉进行收缩研究。
记录了对氯化钾（15 - 90 mM）和去氧肾上腺素（10⁻⁹ - 10⁻⁴ M）的收缩反应。与Sham大鼠相比，门静脉结扎大鼠的血管反应性和敏感性均显著降低。长期硝酸异山梨酯治疗可降低门静脉结扎大鼠的门静脉压力。此外，硝酸异山梨酯治疗后，门静脉结扎大鼠和Sham大鼠对氯化钾和去氧肾上腺素的最大收缩反应均显著增强，但门静脉结扎大鼠仍存在相对反应低下。相比之下，单剂量硝酸异山梨酯对门静脉结扎大鼠或Sham大鼠对氯化钾或去氧肾上腺素的收缩敏感性或反应性均无改变。
我们的结果表明，长期给予硝酸异山梨酯可增强门静脉结扎大鼠和Sham大鼠的血管收缩性，但门静脉结扎大鼠仍存在相对反应低下。
