腎Adenosinetriphosphataseに依る実験高血圧(第2報) : Post腎Adenosinetriphosphatase高血圧及びその脈管変化

Previous experiment showed that repeated intravenous injections of dialyzed Kidney-ATPase had a pressor effect in dogs after each injection, and that they produced degenerative and proliferative changes of arterial and arteriolar walls, but did not produce a sustained hypertension.Attempting to induce a sustained hypertension by repeated injections of dialyzed Kidney-ATPase, further investigation was performed.Four adult mongrel dogs of 9 to 13 kg. body weight, two male and two female, were used. Two of them were nephrectomized unilaterally prior to this experiment. One unilaterally nephrectomized and one normal were treated with dialyzed Kidney-ATPase only, and the other two dialyzed Kidney-ATPase and choleterol. Dialyzed Kidney-ATPase was given intravenously in dose of 30 to 50 c.c. daily. 50mg. of cholesterol daily was given intravenously for the first two months. After its discontinuance, one of them was treated again with 200 mg. of cholesterol for one month.All four animals were loaded daily with 5 to 15gm. of NaCl in diet and 30 cc. of 1 Mol salt solution intravenously.In the course of this experiment, following studies were performed ; direct measurement of mean arterial pressure by mercury manometer on the femoral artery, renal PAH, sodium thiosulfate and Na clearance, plasma sodium level, electrocardiography, electrophoretic analysis of plasma protein, hematological examination, ATP content and activity of ATPase in blood, and 17-Ketosteroid in urine.After experiment animals were killed by bleeding. At autopsy tissues were taken from heart, aorta, lung, liver, pancreas, intestine, kidney and adrenal. These tissues were fixed in 10% formalin solution, embedded in paraffin, sectioned and stained by hematoxylin-eosin. Tissues of the heart and aorta were stained by Weigert-VanGieson method, and adrenals were studied histochemically.The results were as follows : In the two dogs without cholesterol loading, a sustained hypertension was produced Elevation of mean arterial pressure in these animals was on the average 20 mm. Hg and 10 mm. Hg respectively. In the other two treated with Kidney-ATPase and cholesterol, a sustained elevation of the pressure was not attained although the blood pressure rose after each injection. The latter animals showed an elevation of β₁-globulin in blood plasma, an increase of RBC count and a depression of ST and T in electrocardiogram. It appeared that the Kidney-ATPase increased RPF and GFR in the earlier stage and, that it also increased the sodium reabsorption rate of tubuli. Although ATP content in RBC decreased, that in the whole blood showed variable changes. The amount of Ca^·· and Na^· activated ATPase in blood plasma was increased in three dogs examined.17-KS content in urine did not relate to the blood pressure.The following changes were observed microscopically. In the heart there were intimal and medial thickening with degeneration of the coronary arteries, and intimal thickening and cell infiltration of the arterioles.These histological changes were most prominent in the dog treated with 200mg. of cholesterol and Kidney-ATPase.The aorta of three dogs examined showed focal loss of medial elastic tissue.In the kidney, cell infiltration around the vas afferens, thickening and degeneration of the arterioles were commonly observed. Degeneration and capsular thickening of glomeruli, inclusion of hyaline substance in the capsular space, and degeneration of the tubuli were occasionally found. Histochemical studies of the adrenal showed hyperplasia of zona fasciculata in all four dogs independent with the development of hypertension.