Goldsmith S R, Hasking G J, Miller E
Hennepin County Medical Center, Cardiology Division, Minneapolis, Minnesota 55415.
J Am Coll Cardiol. 1993 Apr;21(5):1107-13. doi: 10.1016/0735-1097(93)90232-p.
This study was designed to determine the effects of intravenous angiotensin II infusions and the short-term effects of enalaprilat on venous plasma norepinephrine and norepinephrine spillover in patients with stable chronic congestive heart failure.
Angiotensin II has been shown experimentally to stimulate norepinephrine release. Such effects, if present in humans with congestive heart failure, could be of pathophysiologic and pharmacologic importance.
In study 1, 60-min angiotensin II (5 ng/kg per min) infusions were administered in eight patients with chronic New York Heart Association functional class II and III congestive heart failure. Heart rate, arterial pressure, forearm venous plasma norepinephrine, norepinephrine clearance (estimated from the clearance of tritiated norepinephrine) and norepinephrine spillover were measured after 30 min in the supine position and after 15 min each of head-up and head-down tilt. All patients were studied in a double-blind manner on two occasions with vehicle control infusions. In study 2, 14 patients comparable to those in the first study had similar measurements made in the supine position before and 30 and 60 min after the administration of enalaprilat (1 mg intravenously). Eight patients received a double-blind vehicle control.
In study 1, there were no effects of angiotensin II on heart rate, plasma norepinephrine, norepinephrine clearance or norepinephrine spillover compared with the vehicle control when the patient was in the supine position. Mean arterial pressure increased from 85 +/- 13 to 95 +/- 10 mm Hg with angiotensin II. During upright tilt, plasma norepinephrine and norepinephrine spillover increased comparably with angiotensin II and the vehicle control. During head-down tilt, plasma norepinephrine decreased with both angiotensin II and the vehicle control. Norepinephrine spillover remained elevated relative to control values on both study days during head-down tilt. In study 2, both enalaprilat and vehicle control administration were associated with a slight decrease in mean arterial pressure (5 +/- 2 vs. 3 +/- 4 mm Hg, p = NS), but no changes were seen in plasma norepinephrine. Norepinephrine clearance and spillover decreased comparably with time after both enalaprilat and vehicle control.
Neither the infusion of angiotensin II nor the acute administration of enalaprilat significantly alters the activity of the sympathetic nervous system as reflected by plasma norepinephrine or systemic venous norepinephrine spillover in patients with chronic congestive heart failure. These data weaken the hypothesis that angiotensin II is an important regulator of sympathetic activity in congestive heart failure.
本研究旨在确定静脉输注血管紧张素II的作用以及依那普利拉对稳定的慢性充血性心力衰竭患者静脉血浆去甲肾上腺素和去甲肾上腺素溢出的短期影响。
实验表明血管紧张素II可刺激去甲肾上腺素释放。这种作用若在充血性心力衰竭患者中存在，可能具有病理生理学和药理学意义。
在研究1中，对8例纽约心脏协会心功能II级和III级的慢性充血性心力衰竭患者进行60分钟的血管紧张素II（5纳克/千克每分钟）输注。在仰卧位30分钟后以及头高位和头低位倾斜各15分钟后，测量心率、动脉压、前臂静脉血浆去甲肾上腺素、去甲肾上腺素清除率（根据氚标记去甲肾上腺素的清除率估算）和去甲肾上腺素溢出。所有患者均以双盲方式在两次实验中接受对照输注。在研究2中，14例与第一项研究中的患者相似的患者，在静脉注射依那普利拉（1毫克）前、给药后30分钟和60分钟时在仰卧位进行类似测量。8例患者接受双盲对照输注。
在研究1中，与对照输注相比，当患者处于仰卧位时，血管紧张素II对心率、血浆去甲肾上腺素、去甲肾上腺素清除率或去甲肾上腺素溢出均无影响。血管紧张素II使平均动脉压从85±13毫米汞柱升至95±10毫米汞柱。在直立倾斜期间，血管紧张素II和对照输注时血浆去甲肾上腺素和去甲肾上腺素溢出的增加程度相当。在头低位倾斜期间，血管紧张素II和对照输注时血浆去甲肾上腺素均下降。在头低位倾斜的两个研究日中，去甲肾上腺素溢出相对于对照值均保持升高。在研究2中，依那普利拉和对照输注均使平均动脉压略有下降（5±2对3±4毫米汞柱，p=无显著性差异），但血浆去甲肾上腺素未见变化。依那普利拉和对照输注后，去甲肾上腺素清除率和溢出均随时间下降程度相当。
在慢性充血性心力衰竭患者中，无论是输注血管紧张素II还是急性给予依那普利拉，均未显著改变交感神经系统的活性，这可通过血浆去甲肾上腺素或全身静脉去甲肾上腺素溢出反映出来。这些数据削弱了血管紧张素II是充血性心力衰竭交感神经活性重要调节因子的假说。
