Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Korea.
Am J Physiol Heart Circ Physiol. 2010 Dec;299(6):H1782-9. doi: 10.1152/ajpheart.00438.2010. Epub 2010 Sep 24.
Urotensin II (UII) is a vasoactive peptide with potent cardiovascular effects through a G protein-coupled receptor. Hypoxia stimulates the secretion of UII and atrial natriuretic peptide (ANP). However, the effect of UII on hypoxia-induced cardiac hypertrophy is still controversial. The present study was conducted to determine whether human UII (hUII)-mediated ANP secretion influences hypoxia-induced cardiac hypertrophy using in vitro and in vivo models. Hypoxia caused an increase in ANP secretion and a decrease in atrial contractility in isolated perfused beating rat atria. hUII (0.01 and 0.1 nM) attenuated hypoxia-induced ANP secretion without changing the atrial contractility, and the hUII effect was mediated by the UII receptor signaling involving phospholipase C, inositol 1,3,4 trisphosphate receptor, and protein kinase C. Rats treated with monocrotaline (MCT, 60 mg/kg) showed right ventricular hypertrophy with increases in pulmonary arterial pressure and its diameter and plasma levels of UII and ANP that were attenuated by the pretreatment with an UII receptor antagonist, urantide. An acute administration of hUII (5 μM injection plus 2.5 μM infusion for 15 min) decreased the plasma ANP level in MCT-treated rats but increased the plasma ANP level in MCT plus urantide-treated and sham-operated rats. These results suggest that hUII may deteriorate MCT-induced cardiac hypertrophy mainly through a vasoconstriction of the pulmonary artery and partly through the suppression of ANP secretion.
尾加压素 II（UII）是一种具有强大心血管作用的血管活性肽，通过 G 蛋白偶联受体发挥作用。缺氧可刺激 UII 和心钠肽（ANP）的分泌。然而，UII 对缺氧诱导的心肌肥厚的影响仍存在争议。本研究旨在使用体外和体内模型确定 UII 是否通过介导 ANP 分泌影响缺氧诱导的心肌肥厚。缺氧可引起分离的灌流跳动大鼠心房中 ANP 分泌增加和心房收缩力下降。UII（0.01 和 0.1 nM）可减轻缺氧诱导的 ANP 分泌，而不改变心房收缩力，UII 作用是通过 UII 受体信号转导介导的，涉及磷脂酶 C、三磷酸肌醇受体和蛋白激酶 C。给予单环毛蚓毒素（MCT，60mg/kg）的大鼠出现右心室肥厚，肺动脉压力及其直径增加，血浆 UII 和 ANP 水平升高，而 UII 受体拮抗剂 urantide 预处理可减轻这些变化。急性给予 UII（5μM 注射加 15min 2.5μM 输注）可降低 MCT 处理大鼠的血浆 ANP 水平，但可增加 MCT 加 urantide 处理和假手术处理大鼠的血浆 ANP 水平。这些结果表明，UII 可能主要通过肺动脉收缩和部分通过抑制 ANP 分泌使 MCT 诱导的心肌肥厚恶化。
