Moreno L, Martínez-Cuesta M A, Piqué J M, Bosch J, Esplugues J V
Department of Pharmacology, Faculty of Medicine, University of Valencia, Spain.
Naunyn Schmiedebergs Arch Pharmacol. 1996 Oct;354(4):474-80. doi: 10.1007/BF00168439.
The present study evaluates the effects of pre-hepatic portal hypertension, induced in rats by partial portal vein ligation, on the responsiveness of rostral (proximal) and caudal (distal) rings from the mesenteric vein. The anatomical origin of the sample influenced the response to vasoconstrictors in sham-operated animals, and this pattern of reactivity was specifically modified in portal-ligated rats. In veins from sham-operated rats, contraction induced by a submaximal concentration of KCl (60 mM) was greater in proximal than in distal rings. Vasopressin and 5-hydroxytryptamine contracted mainly distal rings, methoxamine showed a greater effect on proximal rings, and endothelin-1 and angiotensin-II contracted vein rings independently of their anatomical origin. In veins from portal hypertensive rats, response to KCl (60 mM) were increased in distal rings, and all rings exhibited enhanced reactivity to vasopressin and 5-hydroxyptyptamine as well as attenuation of the response to methoxamine. Responses to endothelin-1 were decreased in proximal vein rings from portal hypertensive rats whereas responses to angiotensin-II were not influenced by the anatomical origin. Incubation with atropine, propranolol or indomethacin, did not modify the responses to vasopressin and 5-hydroxytryptamine in tissues from either sham-operated or portal hypertensive animals. Likewise, the hyporeactivity to methoxamine and endothelin-1 in rings from portal hypertensive rats persisted in the presence of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester. These results suggest the physiological existence of anatomical differences in the responsiveness to vasoconstrictors throughout the mesenteric vein and that changes in the responsiveness of the mesenteric vein induced by portal hypertension are specific for each agonist and possibly result from individual variations at a receptor or post-receptor level.
本研究评估了部分门静脉结扎诱导大鼠产生的肝前性门静脉高压对肠系膜静脉头端(近端)和尾端(远端)血管环反应性的影响。样本的解剖学来源影响了假手术动物对血管收缩剂的反应,而这种反应模式在门静脉结扎大鼠中发生了特异性改变。在假手术大鼠的静脉中,次最大浓度氯化钾(60 mM)诱导的收缩在近端血管环比在远端血管环中更大。血管加压素和5-羟色胺主要使远端血管环收缩,甲氧明对近端血管环的作用更大,而内皮素-1和血管紧张素-II使静脉血管环收缩,与它们的解剖学来源无关。在门静脉高压大鼠的静脉中,远端血管环对氯化钾(60 mM)的反应增强,所有血管环对血管加压素和5-羟色胺的反应性均增强,而对甲氧明的反应减弱。门静脉高压大鼠近端静脉环对内皮素-1的反应减弱,而对血管紧张素-II的反应不受解剖学来源的影响。用阿托品、普萘洛尔或吲哚美辛孵育,不会改变假手术或门静脉高压动物组织对血管加压素和5-羟色胺的反应。同样,在一氧化氮抑制剂NG-硝基-L-精氨酸甲酯存在的情况下,门静脉高压大鼠血管环对甲氧明和内皮素-1的低反应性仍然存在。这些结果表明,在整个肠系膜静脉中,对血管收缩剂的反应性在生理上存在解剖学差异,并且门静脉高压诱导的肠系膜静脉反应性变化对每种激动剂都是特异性的,可能是由受体或受体后水平的个体差异导致的。