Physiological and biochemical evidence for coordinate increases in muscarinic receptors and Gi during pacing-induced heart failure.
Physiological and biochemical evidence for coordinate increases in muscarinic receptors and Gi during pacing-induced heart failure.
复制标题
起搏引起的心力衰竭期间毒蕈碱受体和 Gi 协调增加的生理和生化证据。
DOI：
10.1161/01.cir.94.1.102
复制
发表时间：
1996
期刊：
影响因子：
37.8
通讯作者：
Vatner,SF
中科院分区：
文献类型：
--
作者：
Vatner,DE;Sato,N;Galper,JB;Vatner,SF
心肌鸟苷酸抑制蛋白（Gi）的增加，在心力衰竭中经常观察到，是否与任何功能效应有关尚不清楚。方法和结果8只假手术犬和10只起搏诱导的心力衰竭犬进行了研究（240 bpm，持续4至7周），其特征为左心室dP/dt降低（P<0.05）（从2926±99降至1303±126 mm Hg/s）。毒蕈碱激动剂乙酰胆碱（10 μg/kg IV）在存在神经节阻滞的情况下使心力衰竭时的左心室dP/dt（-23 ±2%）比心力衰竭前（-8 ±2%）降低更多（P<0.05），尽管动脉压降低较少。心力衰竭时Giα 2增加55%。卡巴胆碱（10− 8 ~ 10− 3 mol/L）抑制异丙肾上腺素刺激的腺苷酸环化酶的剂量反应曲线显示，与假手术犬相比，卡巴胆碱对心力衰竭的抑制作用显著更强（P<0.05）。与假手术犬（124±7.4 fmol/mg蛋白质）相比，心力衰竭犬（153±6.2 fmol/mg蛋白质）的这些变化与毒蕈碱受体密度的协同增加有关，这是通过拮抗剂与3 H-奎宁环基二苯甲酸酯的结合测定的。激动剂与卡巴胆碱的结合也揭示了心力衰竭中总毒蕈碱受体的增加，而高亲和力和低亲和力受体的分数没有变化。提供了生理和生化证据来支持这样的概念，即心力衰竭中毒蕈碱受体数量和Gilevels的协同增加与腺苷酸环化酶活性的抑制增加和腺苷酸环化酶活性的抑制增加有关。心肌收缩力
BackgroundIt is not clear whether the increase in the myocardial guanylyl nucleotide inhibitory protein (Gi), frequently observed in heart failure, is associated with any functional effects.Methods and ResultsEight sham-operated dogs and 10 dogs were studied with pacing-induced heart failure (240 bpm for 4 to 7 weeks), characterized by reduced (P<.05) left ventricular dP/dt (from 2926±99 to 1303±126 mm Hg/s). The muscarinic agonist acetylcholine (10 μg/kg IV) in the presence of ganglionic blockade reduced left ventricular dP/dt more (P<.05) in heart failure (−23±2%) than before heart failure (−8±2%), despite lesser reductions in arterial pressure. Giα2was increased by 55% in heart failure. Dose-response curves for carbachol (10−8to 10−3mol/L) inhibition of isoproterenol-stimulated adenylyl cyclase demonstrated significantly greater (P<.05) inhibition in heart failure compared with sham-operated dogs. These changes were associated with a coordinate increase in muscarinic receptor density, determined by antagonist binding with3H-quinuclidinyl benzilate, in heart failure (153±6.2 fmol/mg protein) compared with sham-operated dogs (124±7.4 fmol/mg protein). Agonist binding with carbachol also revealed an increase in total muscarinic receptors in heart failure without a change in fraction of high- and low-affinity receptors.ConclusionsThese data, in the aggregate, provide physiological and biochemical evidence to support the concept that the coordinate increases in muscarinic receptor number and Gilevels in heart failure are coupled to increased inhibition of adenylyl cyclase activity and an increased inhibition of myocardial contractility.