Steinhelper M E, Cochrane K L, Field L J
Cold Spring Harbor Laboratory, NY 11724.
Hypertension. 1990 Sep;16(3):301-7. doi: 10.1161/01.hyp.16.3.301.
Chronic regulation of the cardiovascular system by atrial natriuretic factor was investigated by generating transgenic mice with elevated hormone levels in the systemic circulation. A fusion gene comprising the mouse transthyretin promoter and mouse atrial natriuretic factor structural sequences was designed so as to target hormone expression to the liver. Hepatic expression of atrial natriuretic factor was detectable as early as embryonic day 15 in transgenic animals. In adult transgenic mice, plasma immunoreactive atrial natriuretic factor concentration was elevated at least eightfold as compared with nontransgenic littermates. The mean arterial pressure of conscious transgenic mice was 75.5 +/- 0.9 mm Hg, significantly less than that of nontransgenic siblings (103.9 +/- 2.0 mm Hg). This difference in mean arterial pressure was not accompanied by significant changes in several other physiological parameters, including heart rate, plasma and urinary electrolytes, water intake, and urine volume. This study demonstrates that a chronic elevation of plasma atrial natriuretic factor decreases arterial blood pressure without inducing diuresis and natriuresis in transgenic mice and also illustrates the value of the transgenic approach for the study of the cardiovascular system.
通过培育全身循环中激素水平升高的转基因小鼠，研究了心房利钠因子对心血管系统的慢性调节作用。设计了一种包含小鼠转甲状腺素蛋白启动子和小鼠心房利钠因子结构序列的融合基因，以便将激素表达靶向肝脏。在转基因动物中，早在胚胎第15天就能检测到心房利钠因子的肝脏表达。在成年转基因小鼠中，血浆免疫反应性心房利钠因子浓度比非转基因同窝小鼠至少升高了八倍。清醒转基因小鼠的平均动脉压为75.5±0.9毫米汞柱，明显低于非转基因同胞小鼠（103.9±2.0毫米汞柱）。平均动脉压的这种差异并没有伴随着其他几个生理参数的显著变化，包括心率、血浆和尿液电解质、水摄入量和尿量。这项研究表明，血浆心房利钠因子的慢性升高可降低转基因小鼠的动脉血压，而不会诱导利尿和利钠，同时也说明了转基因方法在心血管系统研究中的价值。
