Rose C E, Latham L B, Brashers V L, Rose K Y, Sandridge M P, Carey R M, Althaus J S, Miller E D
Department of Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Am J Physiol. 1988 Jan;254(1 Pt 2):H72-80. doi: 10.1152/ajpheart.1988.254.1.H72.
The role of endogenous opioids in systemic and renal circulatory changes during combined acute hypoxemia and hypercapnic acidosis was evaluated in seven conscious female mongrel dogs in rigid sodium balance. Animals were studied 2 wk apart in separate protocols of combined acute hypoxemia (arterial O2 tension = 33 +/- 1 mmHg) and hypercapnic acidosis (arterial CO2 tension = 56 +/- 1 mmHg, pH = 7.19 +/- 0.01) of 40 min duration during 1) naloxone, 5 mg/kg iv bolus followed by an intravenous infusion of 5 mg.kg-1.h-1, and 2) vehicle (5% dextrose in water) alone. Systemic circulatory changes during the combined acute blood-gas derangement including increased mean arterial pressure, heart rate, and cardiac output and decreased total peripheral resistance were comparable between naloxone and vehicle treatments. However, in striking contrast to the brief fall in renal hemodynamic function during combined acute hypoxemia and hypercapnic acidosis with vehicle, naloxone administration during the combined acute blood-gas derangement resulted in a sustained decrease in effective renal plasma flow, glomerular filtration rate, and filtered sodium load and enhanced rise in circulating norepinephrine and epinephrine. Changes in plasma renin activity were comparable between vehicle and naloxone protocols except that plasma renin activity increased from the first to the second 20-min periods of combined hypoxemia and hypercapnic acidosis with naloxone. These observations suggest that endogenous opioids may contribute to preservation of renal hemodynamic function during acute blood-gas derangements, possibly through attenuation of sympathetic nervous system and renin-angiotension activation.
在七只维持严格钠平衡的清醒雌性杂种犬中，评估了内源性阿片类物质在急性低氧血症和高碳酸性酸中毒合并发生时对全身和肾脏循环变化的作用。动物在单独的实验方案中，每隔2周接受一次实验，实验包括持续40分钟的急性低氧血症（动脉血氧分压=33±1mmHg）和高碳酸性酸中毒（动脉血二氧化碳分压=56±1mmHg，pH=7.19±0.01），实验分两组进行：1）静脉注射5mg/kg的纳洛酮推注，随后以5mg·kg-1·h-1的速度静脉输注；2）仅给予赋形剂（5%葡萄糖水溶液）。在急性血气紊乱合并发生期间，全身循环变化包括平均动脉压升高、心率加快、心输出量增加和总外周阻力降低，纳洛酮治疗组和赋形剂治疗组之间具有可比性。然而，与给予赋形剂时急性低氧血症和高碳酸性酸中毒合并发生期间肾脏血液动力学功能短暂下降形成鲜明对比的是，在急性血气紊乱合并发生期间给予纳洛酮导致有效肾血浆流量、肾小球滤过率和滤过钠负荷持续下降，并使循环中的去甲肾上腺素和肾上腺素进一步升高。赋形剂组和纳洛酮组之间血浆肾素活性的变化具有可比性，只是在纳洛酮治疗的急性低氧血症和高碳酸性酸中毒合并发生的第一个20分钟到第二个20分钟期间，血浆肾素活性有所增加。这些观察结果表明，内源性阿片类物质可能有助于在急性血气紊乱期间维持肾脏血液动力学功能，可能是通过减弱交感神经系统和肾素-血管紧张素激活来实现的。
