Plante G E, Prévost C, Sirois P, Rochat C, Prost J F
Department of Physiology, University of Sherbrooke, Canada.
J Pharmacol Exp Ther. 1989 Feb;248(2):741-6.
Tertatolol is a new beta-adrenergic blocking agent that possesses unique actions on kidney function. In the present study, the effect of increasing doses of tertatolol (0.025, 0.05, 0.1, 0.2 and 0.3 mg) was examined in different groups of anesthetized rats and the results compared with injection of the vehicle. Bolus i.v. injections of tertatolol resulted in a dose-related elevation of urine volume (UV), from 4.1 +/- 0.3 to 6.0 +/- 0.4, 10.2 +/- 1.3, 13.8 +/- 1.2, 18.8 +/- 1.9 and 16.4 +/- 1.8 microliters/min, respectively. Similarly, urine Na increased from 0.4 +/- 0.1 to 0.8 +/- 0.2, 1.2 +/- 0.2, 2.2 +/- 0.3, 3.4 +/- 0.7 and 2.9 +/- 0.6 mueq/min. These changes were associated with a progressive rise in glomerular filtration rate (GFR) from a mean control value of 1.15 +/- 0.10 to 1.28 +/- 0.09, 1.41 +/- 0.07, 1.50 +/- 0.10, 1.62 +/- 0.16 and 1.48 +/- 0.07 ml/min. No change in urinary phosphate excretion was observed. In a separate group of studies, the effect of tertatolol was compared with propranolol (1 mg): the maximal elevation on UV and urine Na was less than 25% of that obtained with tertatolol. Elevation of GFR was also 30% higher in animals receiving tertatolol. The effect of tertatolol on UV and urine Na resulted in part from the rise in GFR but also from tubular inhibition of Na transport, since fractional Na excretion increased from 0.24 +/- 0.09 to a maximal value of 1.76 +/- 0.10%. This tubular action presumably occurs beyond the proximal nephron, because no effect on urinary phosphate excretion was obtained during tertatolol.(ABSTRACT TRUNCATED AT 250 WORDS)
特他洛尔是一种新型β-肾上腺素能阻滞剂,对肾功能具有独特作用。在本研究中,对不同组麻醉大鼠给予递增剂量的特他洛尔(0.025、0.05、0.1、0.2和0.3毫克),并将结果与注射溶媒进行比较。静脉推注特他洛尔导致尿量(UV)呈剂量依赖性升高,分别从4.1±0.3升至6.0±0.4、10.2±1.3、13.8±1.2、18.8±1.9和16.4±1.8微升/分钟。同样,尿钠从0.4±0.1升至0.8±0.2、1.2±0.2、2.2±0.3、3.4±0.7和2.9±0.6微当量/分钟。这些变化与肾小球滤过率(GFR)从平均对照值1.15±0.10逐渐升至1.28±0.09、1.41±0.07、1.50±0.10、1.62±0.16和1.48±0.07毫升/分钟相关。未观察到尿磷排泄变化。在另一组研究中,将特他洛尔的作用与普萘洛尔(1毫克)进行比较:UV和尿钠的最大升高幅度小于特他洛尔的25%。接受特他洛尔的动物中GFR的升高也高出30%。特他洛尔对UV和尿钠的作用部分源于GFR的升高,但也源于肾小管对钠转运的抑制,因为钠排泄分数从0.24±0.09升至最大值1.76±0.10%。这种肾小管作用可能发生在近端肾单位之后,因为在特他洛尔给药期间未获得对尿磷排泄的影响。(摘要截取自250字)