Sakamoto S, Liang C S
Department of Medicine, University of Rochester Medical Center, New York 14642.
Circulation. 1989 Oct;80(4):1010-5. doi: 10.1161/01.cir.80.4.1010.
The endogenous opiate system is activated in congestive heart failure. because endogenous opioids are known to depress the baroreflex function, we conducted studies to determine whether the increased endogenous opioids play a role in causing the reduced baroreflex function that occurs in heart failure. Right-sided congestive heart failure was produced in 16 dogs by tricuspid avulsion and progressive pulmonary artery constriction. Seven sham-operated dogs were included for comparison. Baroreflex function was measured in the conscious dogs after pretreatment with either normal saline or an opiate-receptor antagonist by bolus administration of phenylephrine. The slope of the regression line relating systolic blood pressure to cardiac cycle (R-R) interval was taken as an index of baroreflex sensitivity. Plasma beta-endorphin was elevated in the dogs with heart failure (15.3 +/- 2.5 pmol/l) compared with the sham-operated dogs (4.2 +/- 0.4 pmol/l, p less than 0.001). The dogs with heart failure also exhibited a reduced baroreflex sensitivity (3.84 +/- 0.19 msec/mm Hg) after saline pretreatment when compared with the sham-operated dogs (10.86 +/- 1.20 msec/mm Hg, p less than 0.001). Administration of naloxone hydrochloride increased the baroreflex sensitivity of dogs with heart failure to 5.16 +/- 0.26 msec/mm Hg (p less than 0.01) but produced no significant effects in sham-operated dogs (11.36 +/- 1.42 msec/mm Hg). To further study the site of action for the effect of naloxone, we measured baroreflex sensitivity in the dogs with heart failure after pretreatment with naloxonazine, a selective mu-receptor antagonist, with ICI 154,129, a selective delta-receptor antagonist, or with naloxone methobromide, a quaternary analogue of naloxone that does not penetrate the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
内源性阿片系统在充血性心力衰竭时被激活。由于已知内源性阿片类物质会抑制压力反射功能，我们开展了研究以确定内源性阿片类物质增加是否在导致心力衰竭时出现的压力反射功能降低中起作用。通过三尖瓣撕脱和渐进性肺动脉缩窄在16只犬中制造右侧充血性心力衰竭。纳入7只假手术犬作为对照。在用生理盐水或阿片受体拮抗剂预处理后，通过推注去氧肾上腺素在清醒犬中测量压力反射功能。将收缩压与心动周期（R-R）间期的回归线斜率作为压力反射敏感性的指标。与假手术犬（4.2±0.4 pmol/l，p<0.001）相比，心力衰竭犬的血浆β-内啡肽升高（15.3±2.5 pmol/l）。与假手术犬（10.86±1.20 msec/mm Hg，p<0.001）相比，心力衰竭犬在生理盐水预处理后也表现出压力反射敏感性降低（3.84±0.19 msec/mm Hg）。给予盐酸纳洛酮可使心力衰竭犬的压力反射敏感性增加至5.16±0.26 msec/mm Hg（p<0.01），但对假手术犬（11.36±1.42 msec/mm Hg）无显著影响。为进一步研究纳洛酮作用的位点，我们在用选择性μ受体拮抗剂纳洛嗪、选择性δ受体拮抗剂ICI 154,129或不能穿透血脑屏障的纳洛酮甲溴化物（纳洛酮的季铵类似物）预处理后，测量了心力衰竭犬的压力反射敏感性。（摘要截断于250字）
