Poulos J E, Gower W R, Sullebarger J T, Fontanet H L, Vesely D L
Department of Biochemistry, James A. Haley Veterans Hospital, Tampa, FL 33612, USA.
Cardiovasc Res. 1996 Nov;32(5):909-19.
The present investigation was designed to determine if atrial natriuretic peptide (ANP) gene expression increases in extracardiac as well as within the heart in congestive heart failure.
Congestive heart failure (CHF) was induced by producing cardiac hypertrophy secondary to an aortocaval fistula in Sprague-Dawley rats. To characterize this model, control and CHF rats had cardiac catheterizations and transthoracic echocardiography. ANP messenger RNA was measured by RNAase protection analysis in atria, ventricles, liver, colon, and stomach of CHF and sham rats and quantitated by 2-D scanning. The product of ANP gene expression was determined in each of these tissues with high performance-gel permeation chromatography. To help determine if increased degradation of atrial natriuretic peptides occur in congestive heart failure, the circulating concentrations and the excretion of the atrial natriuretic peptides into urine were measured by specific radioimmunoassays.
ANP steady-state mRNA increased 4.2 +/- 0.05 and 4.3 +/- 0.06-fold, respectively, in the antrum of the stomach and within the heart ventricle of CHF rats compared with age-matched sham rats. ANP gene expression was present but not increased in atria, liver, and gastrointestinal tract of the CHF rats. High-performance gel permeation chromatography revealed that the product of this ANP gene expression within the stomach and heart ventricle in CHF animals was the ANP prohormone. There was not any decrease in the metabolism of these peptides by the kidney in CHF.
ANP steady-state mRNA increases in extracardiac (i.e., stomach antrum) tissue as well as in the ventricle of the heart in CHF. The product of the ANP gene expression, i.e., the ANP prohormone is the same in the extracardiac tissues as within the heart. Whether the increased extracardiac ANP steady-state mRNA and its resultant increased atrial natriuretic peptides helps prevent bowel wall edema in CHF needs to be elucidated.
本研究旨在确定充血性心力衰竭时，心外组织以及心脏内的心房利钠肽（ANP）基因表达是否增加。
通过在Sprague-Dawley大鼠中制造继发于主动脉腔静脉瘘的心脏肥大来诱导充血性心力衰竭（CHF）。为了表征该模型，对对照大鼠和CHF大鼠进行了心导管检查和经胸超声心动图检查。通过RNA酶保护分析测量CHF大鼠和假手术大鼠的心房、心室、肝脏、结肠和胃中的ANP信使RNA，并通过二维扫描进行定量。用高效凝胶渗透色谱法测定这些组织中每个组织的ANP基因表达产物。为了帮助确定充血性心力衰竭时心房利钠肽的降解是否增加，通过特异性放射免疫测定法测量循环浓度和心房利钠肽向尿液中的排泄量。
与年龄匹配的假手术大鼠相比，CHF大鼠胃窦和心室内的ANP稳态mRNA分别增加了4.2±0.05倍和4.3±0.06倍。CHF大鼠的心房、肝脏和胃肠道中存在ANP基因表达，但未增加。高效凝胶渗透色谱显示，CHF动物胃和心室内该ANP基因表达的产物是ANP前体激素。CHF时肾脏对这些肽的代谢没有任何降低。
CHF时心外组织（即胃窦）以及心脏心室中的ANP稳态mRNA增加。心外组织中ANP基因表达的产物，即ANP前体激素与心脏内的相同。心外ANP稳态mRNA增加及其导致的心房利钠肽增加是否有助于预防CHF中的肠壁水肿，有待阐明。
