Reversibility of acid-activation and cryoactivation of inactive renin in human plasma.
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Biomedical subjects
Publications and source records attributed to C H Pak.
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The role of the sympathetic nervous system in the mechanism of blood pressure rise in spontaneously hypertensive rats (SHR) was investigated by measuring plasma levels of adrenaline and noradrenaline in 5-week-old, 7-week-old, 6-month-old, and 12-month-old SHR. Age-matched normotensive Wistar-Kyoto rats (WKY) were used as control animals. Blood samples were collected through an indwelling catheter in a conscious state. In 5-week-old and 7-week-old SHR both plasma adrenaline and noradrenaline concentrations were significantly higher than those of WKY. In 6-month-old SHR plasma noradrenaline was significantly higher than that of WKY, while plasma adrenaline was not significantly different. In 12-month-old SHR the plasma levels of both adrenaline and noradrenaline were not different from those of WKY. This study indicated more distinct increase in plasma noradrenaline than in plasma adrenaline in young SHR, and also suggests that peripheral sympathetic activity and the adrenal medulla may play important roles in the development of hypertension in SHR.
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The mechanism of the increase in renin activity in human plasma which had been kept -5 degrees C for 4 days (cryoactivation) was investigated. From the results of clinical studies, it is likely that the controling mechanism of inactive renin has something in common with that of active renin. The experimental data showed that the increase in renin activity of human plasma by cryoactivation was closely correlated to the increase obtained by incubation with trypsin (r = 0.88, p less than 0.001, n = 10). Soybean trypsin inhibitor, aprotinin and di-isopropylfluorophosphate (DFP) inhibited cryoactivation, indicating that the cryoactivation is due to the action of a trypsin-like serine enzyme. Trypsin which had no effect on plasma renin activity in the presence of the same amount of soybean trypsin inhibitor at 37 degrees C, activated the renin activity during cold incubation, suggesting that the dissociation of the trypsin-inhibitor complex may have taken place at a low temperature. Endogenous trypsin inhibitor is also likely to lose its affinity to endogenous trypsin-like enzyme at a low temperature.
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1. The mechanism of increased renin activity after human plasma had been kept at -5 degrees C for 4 days (cryoactivation) was investigated. 2. The increase in renin activity of human plasma by cryoactivation was closely correlated to the increase obtained by incubation with trypsin (r = 0.88, P less than 0.001, n = 10). 3. An inhibitor of thiol enzyme, N-ethylmaleimide did not inhibit cryoactivation. 4. Soyabean trypsin inhibitor and di-isopropylflurophosphate (DFP) inhibited cryoactivation, suggesting that the cryoactivation may be due to the action of a trypsin-like serine enzyme. 5. In an experiment in the rat haemorrhagic shock caused parallel and cryoactivated plasma, the renin activity being about two times higher in the latter. No significant differences were found in the concentrations of renin and renin substrate between the non-cryoactivated and cryoactivated plasma samples. 6. The results may indicate that a destruction of an inhibitor of the renin-renin substrate reaction is responsible for the increase of renin activity after exposure of rat plasma to low temperature. A trypsin-like enzyme in plasma might have destroyed the inhibitor during this procedure.
The effect of chronic oral administration of propranolol (39--80 mg/Kg/day, for 21--27 days) on blood pressure, plasma renin concentration, and heart rate were studied in 2 types of renovascular hypertensive rats; one-kidney type with normal plasma renin and two-kidney type with high plasma renin. No significant change was observed in the blood pressure of either model during the administration of propranolol in spite of a significant reduction of heart rate. Plasma renin concentration showed a trend of suppression in two-kidney type rats, but this change was not significant. There was no suppression in one-kidney type rats. These results suggest that the beta-adrenergic system may not play a major role either in regulating plasma renin level or in maintaining the blood pressure in renovascular hypertensive rats.
Various facets of activation of inactive renin by acidification or cold exposure were investigated in normal human plasma. The acid activation obtained by titration was usually less than that by dialysis method, but varied from 41% to 122% of the latter. The acid phase of acid activation accounted for about 70% of the total activation achieved by the combined effects of the acid and alkaline phases on the average, and was not affected by any of the inhibitors for serine, thiol or carboxyl protease, whereas serine protease inhibitors suppressed the activation of both renin and plasma kallikrein in the alkaline phase of acid activation. A different mode of plasma kallikrein activation suggested some difference in the mechanism between the alkaline phase of acid activation and the cryoactivation. A part of cryoactivation of renin was independent of the action of plasma kallikrein. The renin activated by either acidification or cold exposure without concomitant activation of plasma kallikrein was reinactivated by the removal of pH and temperature, but recovered by repeating acidification or cold exposure. When active plasma kallikrein had been produced, it activated inactive renin irreversibly. It appears unlikely that irreversible activation of inactive renin is taking place in the normal circulation where practically no active plasma kallikrein is present.
We report a case of primary aldosteronism in a 30-year-old woman without hypertension or any other characteristic symptoms. The condition was first suspected by hypokalemia (2.6 mEq/liter), which was incidentally found by routine checkup. There was evidence of suppressed plasma renin activity (PRA) and elevated plasma aldosterone levels. However, the blood pressure never reached a hypertensive level, and the circulating blood volume was within a normal range. A functioning right adrenal tumor was diagnosed by adrenal scintigraphy, computerized x-ray tomography, and adrenal venography. Adrenal venous catheterization suggested an aldosteronoma, which was confirmed by lateralized hypersecretion of aldosterone. After removal of the benign adenoma, the biochemical abnormalities were corrected, yet the blood pressure remained much the same. Hypertension is not necessarily a sign of primary aldosteronism.
Patients suffering from gout and uric acid diathesis received a specialized diet containing 70 g protein (85% of plant protein including 20 g of soybean protein isolate), 85 g fat and 350 g carbohydrates. As a result there was an improvement of the general well-being during dietetic management, a rise of pH of the urine to normal, a decrease in the concentration of uric acid in blood serum and urine with a simultaneous elevation of the latter's clearance, an increase in glomerular filtration, a reduction in blood cholesterol content. The data obtained allow the conclusion to be made about the necessity of the rigid observance of the diet by the patients. This will play an important role both in the treatment and prophylaxis of urolithiasis in the patients' population under consideration.
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