대사성 Acidosis 및 Alkalosis가 신장 및 간장에서의 색소배설에 미치는 영향에 관한 실험적 연구
Certain dyes such as phenol red and chlorphenol red are secreted by the renal tubule much faster than others such as bromphenpol blue and bromcresol green. However, the mechanism(s) for this differential rate of secretion of various homologous dyes is not known at present. Lee and Hong reported that the degree of binding of these dyes to plasma protein is inversely proportinal to the rate of tubular secretion and, on the basis of this finding, suggested that the Tm values for each dye is different, dependent upon the extent of binding of the dye to
plasma protein. This suggestion was based on the earlier report by Ochwadt and Pitts that the Tm value of phenol red increased when plasma protein was replaced by dextran in order to reduce the extent of protein binding.
Similar differences in the rate of tubular secretion are also known to exist among various organic acids such as PAH, diodrast and probenecid. the rate of secretion of PAH is nearly twice that of diodrast while probenecid is very slowly secreted by the tubule although this substance is an powerful competitive inhibiter of the former two compounds. Therefore, probenecid has been considered to be a "refractory" substrate. However, it has been shown resently by Weiner et al. that probenecid excretion increased greatly in alkalosis, and, on the basis of this and
other additional findings, they advanced a new hypo5thesis that probenecid itself is actively secreted in large amounts by the proximal tubule byt is almost completely reabsorbed subsequently in a non-ionic diffusion process by virtue of its great lipid solubility. This non-ionic reabsorption is suppressed when the urine pH increases, for the dissociation of the weak acid becomes more extensive.
In view of this latest hypothesis, it occurred to us that the differential rates of tuvular secretion of various phenol re derivatives also may be partly, if not entirely, due to the fact that, although these dyes are secreted by the proximal tubule to a similar extent, the degree of subsequent reabsorption is quite
different among various dyes. In order to test this hypothesis, a series of experiments were undertaken in artificially induced metabolic acidosis or alkalosis. The biliary excretion was also studied simultaneously in order to make a further comparison between the renal and hepatic transport mechanisms of these
dyes. Moreover, a phthalein dye, bromsulfalein, was also used to see if the excretion of this dye is also modified as is that of phenol red derivatives. It has been shown earlier that the kidney and the liver seem to excrete phenol red derivatives and bromsulfalein through a common, active transport system; yet there are certain quantitative differences between the two organs.
Experiments were carried out in 44 anesthetized female dogs, weighing approximately 10 kgs. Having fasted for 12 to 15 hrs prior to the experiment, the dog was anesthetized with nembutal(27 mg/kg, i.v.). a femoral artery was cannulated for blood sampling and a femoral vein for infusion. The urinary bladder was catheterized. The common bile duct was also cannulated while the cystil duct was ligated.
The metabolic acidosis was induced by the oral administration of HCI(10 mEq/kg) 15 to 18 hrs prior to the onset of experiment. The metabolic alkalosis was induced by a continuous infusion of 0.3 M NaHCO^^3 during the experiment.
30 to 40 min after the above surgical procedures are over, either 0.3 M NaCl(in acidotic group) or 0.3 M NaHCO^^3 (in alkalotic group) was infused at a fast rate(33 ml/min) for a period of 15 min, following which priming doses of inulin(50 mg/kg) and a dye(5 to 25 mg/kg) were given intravenously. Sustained doses of inulin(15 mg/min.) and the dye(0.6 to 2 mg/min) were contained in either 0.3 M NaCl(in acidotic group) or in 0.3 M NaHCO^^3 (in alkalotic group) which was infused at a rate of 5 ml/min until termination of experiment.
There phenol red derivatives, i.e., phenol red(PSP), brompheno blue(BPB) and bromcresol green(GCG) were selected for the study in view of known differences in the rate of urinary and biliary excretion. A phthalein dye, bromsulfalein(BSP), was also used for a comparison.
The results may be summarized as follows:
1. In general, the rate of urinary excretion was greatest in PSP and became less in the oder of BPB, BSP and BCG.
2. Although alkalosis slightly augmented the urinary excretion of phenol red derivatives, it lowered the excretion of BSP.
3. The rate of biliary excretion was greatest in BSP and decreased in the order of BPB, PSP and BCG.
4. The biliary excretion of the dye was practically identical in both acidosis and alkalosis and this was attributed to the fact that the difference in hepatic bile pH between acidosis and alkalosis was very small. However, biliary dye excretion was proportional to the rate of bile flow.
5. The urine pH was apparently proportional to the blood pH, although the urine pH, although the urine pH became more acidic or alkaline than the corresponding blood pH. The hepatic bile pH changed very slightly as compared to the urine pH and the gall bladder acidified bile to a similar extent in both acidosis and alkalosis.
6. Considering these results, it is postulated that this differential rate of urinary excretion of various phenol red derivatives is primarily due to the difference in the rate of tubular secretion rather than due to that in subsequent reabsorption.
7. There seems to be a difference in the excretory mechanism of these dyes between the kinney and the live.
8. Phenol red derivatives and BSP do not seem to be excreted by these organs through an entirely identical excretory mechanism as judged by the difference in excretory rate as well as in response to variations in the blood pH.