Gabel R A, Ranaei R A, Kivlighn S D
Department of Cardiovascular Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA.
J Pharmacol Toxicol Methods. 1996 Dec;36(4):189-97. doi: 10.1016/s1056-8719(96)00112-8.
The purpose of the current experiment was to develop fast and accurate assays for measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). An enzymatic method was developed for the determination of inulin, and a colorimetric method was developed for determination of p-aminohippurate (PAH) in the plasma and urine of rats. These assays are easily automated and do not require the use of radioisotopes or corrosive chemicals. Glomerular filtration rate was measured by the clearance of inulin, and effective renal plasma flow was measured by the clearance of PAH. Blood pressure, heart rate, and renal function (urine volume, electrolytes, GFR, and ERPF) were measured in conscious rats for 1.5 h prior to drug treatment and for 3 h after treatment. Baseline renal function was compared to historical data. Acute changes in GFR and ERPF following administration of the vasoconstrictor peptide endothelin-1 (ET-1) were accurately measured with results similar to those obtained with older methodologies. These new methods offer many advantages over previously described methods by eliminating the use of radioisotopes and harsh chemicals. In addition, these methods can be used with an automated instrument with high accuracy and precision. Therefore, these new methods can be used to accurately determine GFR and ERPF and are sensitive enough to detect acute changes in GFR and ERPF in conscious animals.
当前实验的目的是开发用于测量肾小球滤过率（GFR）和有效肾血浆流量（ERPF）的快速且准确的检测方法。开发了一种酶法用于测定菊粉，并开发了一种比色法用于测定大鼠血浆和尿液中的对氨基马尿酸（PAH）。这些检测方法易于自动化，且不需要使用放射性同位素或腐蚀性化学物质。通过菊粉清除率来测量肾小球滤过率，通过PAH清除率来测量有效肾血浆流量。在药物治疗前1.5小时和治疗后3小时，对清醒大鼠的血压、心率和肾功能（尿量、电解质、GFR和ERPF）进行测量。将基线肾功能与历史数据进行比较。使用血管收缩肽内皮素-1（ET-1）给药后，GFR和ERPF的急性变化被准确测量出来，其结果与使用较旧方法获得的结果相似。这些新方法通过消除放射性同位素和刺激性化学物质的使用，相比先前描述的方法具有许多优势。此外，这些方法可以与具有高精度和高准确度的自动化仪器一起使用。因此，这些新方法可用于准确测定GFR和ERPF，并且灵敏度足以检测清醒动物中GFR和ERPF的急性变化。
