Chintala M S, Jandhyala B S
Department of Pharmacology, University of Houston, TX 77204-5515.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Apr;341(4):357-63. doi: 10.1007/BF00180662.
The efficacy of felodipine, a dihydropyridine calcium entry blocker to restore renal function was investigated in Wiggers model of haemorrhagic shock. Mongrel dogs were anaesthetized with sodium pentobarbital and subjected to haemorrhagic shock by allowing the animals to bleed into a reservoir. After maintaining the hypotensive state (mean blood pressure 40-45 mm Hg) for a period of 150 min, the blood was reinfused and the recovery of the various parameters were monitored for an additional 120 min. These studies were conducted in three different groups of dogs: (A) Solvent control, (B) Felodipine 0.01 mumol/kg i.v., administered 10 min prior to reinfusion of the blood, and (C) Felodipine 0.01 mumol/kg i.v., administered prior to haemorrhage. In all the three groups arterial blood pressure returned to similar basal levels following reinfusion. Felodipine administration prior to haemorrhage or before reinfusion (Group B and C) resulted in a 80-95% recovery in the renal blood flow, 60-65% in the glomerular filtration rate, 150-300% in the urine volume and 80-100% in the urinary sodium and potassium excretions. In the vehicle-treated control group, despite a 45% recovery in the renal blood flow, renal function was not restored following reinfusion. The observations made in these studies suggest that felodipine, an arteriolar dilator which also possesses natriuretic properties, could be clinically useful in the treatment of renal failure in haemorrhagic shock. Prevention of cellular calcium overload during ischaemia and reperfusion by this dihydropyridine derivative, may account for its ability to preserve vascular as well as tubular function.
在出血性休克的维格斯模型中，研究了二氢吡啶类钙通道阻滞剂非洛地平恢复肾功能的疗效。用戊巴比妥钠麻醉杂种狗，让动物向贮血器内失血以造成出血性休克。在维持低血压状态（平均血压40 - 45毫米汞柱）150分钟后，再输血，并在另外120分钟内监测各项参数的恢复情况。这些研究在三组不同的狗中进行：（A）溶剂对照组，（B）在输血前10分钟静脉注射非洛地平0.01微摩尔/千克，以及（C）在出血前静脉注射非洛地平0.01微摩尔/千克。在所有三组中，输血后动脉血压均恢复到相似的基础水平。在出血前或输血前给予非洛地平（B组和C组）可使肾血流量恢复80 - 95%，肾小球滤过率恢复60 - 65%，尿量恢复150 - 300%，尿钠和钾排泄恢复80 - 100%。在溶剂处理的对照组中，尽管肾血流量恢复了45%，但输血后肾功能并未恢复。这些研究中的观察结果表明，非洛地平作为一种具有利钠特性的小动脉扩张剂，在临床上可能对治疗出血性休克中的肾衰竭有用。这种二氢吡啶衍生物在缺血和再灌注期间预防细胞钙超载，可能是其能够维持血管和肾小管功能的原因。
