Lernfelt B, Landahl S, Johansson P, Seligman L, Aberg J
Department of Geriatrics, University of Gothenburg, Sweden.
Eur J Clin Pharmacol. 1998 Oct;54(8):595-601. doi: 10.1007/s002280050520.
To study the influence of age on renal and haemodynamic effects of the calcium antagonist felodipine.
Eight young (mean age 27 years) and eight elderly (mean age 75 years) healthy normotensive subjects were given felodipine intravenously for 120 min aiming at close to therapeutic plasma level concentration. Renal blood flow (RBF) and renal vascular resistance (RVR) was estimated from para-aminohippuric acid (PAH) clearance 51CrEDTA clearance was used to measure glomerular filtration rate (GFR) and used in the calculations of fractional excretion (FE) of electrolytes. Impedance cardiography was performed to assess stroke volume and for the calculation of cardiac output and ejection fraction.
At the end of felodipine infusion, the concentration of felodipine was on average 10.0 nmol x l(-1) in young and 12.0 nmol x l(-1) in elderly subjects (NS). During felodipine infusion blood pressure (BP) decreased from 138/76 to 120/68 in elderly subjects. The BP in young subjects was 126/74 at basal and 125/70 after infusion of felodipine. The systemic and renal vascular resistance decreased to a similar extent in young and elderly subjects after felodipine infusion. Felodipine caused a decrease in systemic vascular resistance from 25.6 to 23.3 in elderly and from 23.8 to 21.8 in the young subjects. Mean values for RVR at baseline and during infusion of felodipine were significantly higher in the elderly (10.1-15.1) than in the young subjects (5.4-6.7). Felodipine reduced RVR by 10% in the young and by 12% in the elderly at the end of infusion. The young subjects had 31% higher GFR than the elderly subjects at the start of infusion. Felodipine infusion did not affect GFR. There were no effects on stroke volume and ejection fraction. An initial natriuretic effect was found after infusion of felodipine in the young subjects. The fractional excretion of all electrolytes tended to increase after both felodipine and placebo, more in the elderly than in the young subjects.
The effects of felodipine on central and renal haemodynamics previously observed in young and middle-aged subjects also seem to exist in the elderly. Volume expansion seems to increase the excretion of electrolytes more in elderly than in young people, and therefore the effect of felodipine on natriuresis is more evident in young subjects.
研究年龄对钙拮抗剂非洛地平肾脏及血流动力学效应的影响。
选取8名年轻（平均年龄27岁）和8名老年（平均年龄75岁）健康血压正常的受试者，静脉输注非洛地平120分钟，目标是达到接近治疗血浆水平的浓度。通过对氨基马尿酸（PAH）清除率估算肾血流量（RBF）和肾血管阻力（RVR），用51CrEDTA清除率测量肾小球滤过率（GFR）并用于计算电解质排泄分数（FE）。进行阻抗心动图检查以评估每搏输出量，并计算心输出量和射血分数。
非洛地平输注结束时，年轻受试者中非洛地平浓度平均为10.0 nmol·L-1，老年受试者中为12.0 nmol·L-1（无显著性差异）。在非洛地平输注期间，老年受试者的血压（BP）从138/76降至120/68。年轻受试者基础血压为126/74，输注非洛地平后为125/70。非洛地平输注后，年轻和老年受试者的全身和肾血管阻力均有相似程度的下降。非洛地平使老年受试者的全身血管阻力从25.6降至23.3，年轻受试者从23.8降至21.8。老年受试者在基线和非洛地平输注期间的RVR平均值（10.1 - 15.1）显著高于年轻受试者（5.4 - 6.7）。输注结束时，非洛地平使年轻受试者的RVR降低10%，老年受试者降低12%。输注开始时，年轻受试者的GFR比老年受试者高31%。非洛地平输注未影响GFR。对每搏输出量和射血分数无影响。年轻受试者输注非洛地平后出现初始利钠效应。非洛地平和安慰剂输注后，所有电解质的排泄分数均有增加趋势，老年受试者增加幅度大于年轻受试者。
先前在年轻和中年受试者中观察到的非洛地平对中枢和肾脏血流动力学的影响在老年受试者中似乎也存在。容量扩张似乎使老年受试者的电解质排泄增加幅度大于年轻受试者，因此非洛地平对利钠作用在年轻受试者中更明显。
