Department of Medicine, Unit of Internal Medicine and Hepatology (UIMH), University of Padova, Padua, Italy.
Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey.
Dig Dis Sci. 2021 Mar;66(3):796-801. doi: 10.1007/s10620-020-06233-2. Epub 2020 Apr 2.
In liver cirrhosis, a marked splanchnic vasodilation causes an increase in portal blood flow, contributing to the development of portal hypertension.
To evaluate if, in experimental cirrhosis, a different vascular reactivity exists between splenic and mesenteric components of the splanchnic circulation.
Liver cirrhosis was induced in Sprague Dawley rats by common bile duct ligation. In sections of splenic and superior mesenteric arteries, cumulative dose-response curves were obtained. mRNA expression of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and prostaglandin I synthase (PTGIS) was evaluated.
In cirrhotic rats, mesenteric but not splenic arteries showed a significant increase in endothelium-dependent relaxation to acetylcholine. In control and cirrhotic rats, COX inhibition alone did not significantly change the response of mesenteric arteries to acetylcholine; after inhibiting also NOS, the relaxation was completely abolished in control but only partially decreased in cirrhotic rats. After the inhibition of COX and NOS, the relaxation to acetylcholine was similarly decreased in splenic arteries from control and cirrhotic animals. The contraction induced by phenylephrine of both mesenteric and splenic arteries was decreased in cirrhotic rats. PTGIS mRNA expression did not differ in splenic and mesenteric arteries from control and cirrhotic rats; in cirrhotic rats, eNOS and iNOS mRNA expression was increased in mesenteric but not in splenic vascular bed.
In cirrhotic rats, a decreased splenic arterial response to vasoconstrictors, rather than an increased response to vasodilators, contributes to splanchnic vasodilation, while in mesenteric arteries also an increased response to vasodilators secondary to, but not only, eNOS and iNOS overexpression, plays a role.
在肝硬化中，明显的内脏血管舒张导致门静脉血流量增加，导致门静脉高压的发展。
评估在实验性肝硬化中，内脏循环的脾和肠系膜成分之间是否存在不同的血管反应性。
通过胆总管结扎在 Sprague Dawley 大鼠中诱导肝硬化。在脾和肠系膜上动脉的部分中，获得累积剂量反应曲线。评估内皮型一氧化氮合酶 (eNOS)、诱导型一氧化氮合酶 (iNOS) 和前列腺素 I 合酶 (PTGIS) 的 mRNA 表达。
在肝硬化大鼠中，肠系膜动脉而非脾动脉对乙酰胆碱的内皮依赖性舒张反应显著增加。在对照和肝硬化大鼠中，单独抑制 COX 并未显著改变肠系膜动脉对乙酰胆碱的反应；抑制 NOS 后，对照大鼠的舒张完全被消除，但肝硬化大鼠的舒张仅部分减少。抑制 COX 和 NOS 后，对照和肝硬化大鼠的脾动脉对乙酰胆碱的舒张均相似减少。两种肠系膜和脾动脉对苯肾上腺素的收缩在肝硬化大鼠中均减少。PTGIS mRNA 表达在对照和肝硬化大鼠的脾和肠系膜动脉中没有差异；在肝硬化大鼠中，eNOS 和 iNOS mRNA 表达在肠系膜血管床中增加，但不在脾血管床中增加。
在肝硬化大鼠中，收缩剂引起的脾动脉反应性降低，而不是舒张剂引起的反应性增加，导致内脏血管舒张，而在肠系膜动脉中，也与 eNOS 和 iNOS 过表达相关但不仅相关的舒张剂反应性增加也发挥作用。
