Clinical science and molecular medicine. Supplement最新文献

1. Indomethacin was administered alone or in addition to either diuretic or propranolol therapy to three groups of patients with essential hypertension on a free sodium diet. 2. Indomethacin administration reduced renin secretion by about 30% in untreated uncomplicated hypertensive patients and by about 75% in those whose renin secretion had either been stimulated or suppressed by maintained diuretic or beta-adrenoreceptor-blockade therapy. 3. Indomethacin administration produced no net effect on blood pressure in untreated patients with uncomplicated hypertension but it blunted or reversed the antihypertensive effect of either diuretic or propranolol therapy. 4. Salt and water retention may be an important factor in the blood pressure-raising effect of indomethacin during diuretic or propranolol therapy: In addition, prostaglandin synthesis may be important in counteracting increased alpha-adrenergic tone, which may limit the blood pressure-lowering effect of beta-adrenoreceptor-blockade. 5. Because of these interactions and their pressor potential indomethacin should be used with caution when combined with either diuretics or beta-adrenoreceptor blockers.

1. Hypoxanthine--guanine phosphoribosyltransferase (HGPRT) activity was measured in erythrocyte haemolysates and quadriceps muscle extracts of normal and dystrophic 129 ReJ and C57 BL/6J mice with [8(-14)C]hypoxanthine as substrate and 5-phosphorylribose 1-pyrophosphate as a ribose 5-phosphate donor. [8(-14)C]Inosine monophosphate formed was separated by high-voltage electrophoresis and radioactivity was measured by liquid-scintillation counting. 2. In erythrocyte haemolysates, HGPRT activity was similar in normal and dystrophic C57 BL/6J mice but was significantly higher in dystrophic than in normal 129 ReJ mice. Elevated enzyme activity was observed only in mice that were clinically severely affected. 3. In muscle homogenates, HGPRT activity was significantly higher in dystrophic than in normal animals of both 129 ReJ and C57 BL/6J mice. Enzyme activity was not related to the severity of the disease. 4. It is suggested that changes in erythrocytes are secondary to the dystrophic process and that elevated HGPRT activity in skeletal muscle may be related to abnormal energy metabolism, possibly via the pentose monophosphate shunt.

1. We have found that 'acid'-activation of inactive human plasma renin is a two-phase process. About 30% of activation occurs during dialysis to pH 3.3; the remaining 70% occurs at alkaline pH. 2. The 'alkaline phase' of activation has a pH optimum between 7.5 and 8.4. It is inhibited by unacidified plasma and by soya-bean or lima-bean trypsin inhibitors. 3. 'Cryoactivation' of inactive plasma renin, which occurs at -4 degrees C and alkaline pH, is also inhibited by soya-bean or lima-bean trypsin inhibitors and by the serine protease inhibitors diisopropylphosphorofluoridate and benzamidine. 4. Thus endogenous neutral serine proteases participate in the activation of inactive plasma renin in vitro. Their action is prevented in the circulation by inhibitors which are inactivated by acid or cold.

1. A patient presented with mild hypertension, a raised plasma total renin concentration but a normal plasma angiotensin II concentration. The discrepancy was due to a high concentration of inactive renin in the plasma. 2. A renal carcinoma was detected and removed. The tumour contained a higher proportion of inactive renin than was found in uninvolved areas of the kidney. After unilateral nephrectomy, the plasma concentration of inactive renin fell to normal. 3. Six months later, plasma inactive renin concentration again increased and a metastasis was detected in a rib. Excision of the rib together with radiotherapy resulted in a fall in plasma inactive renin to normal. 4. The inactive renin in plasma and tumour extracts was activated to the same extent by acid treatment and by trypsin.

1. Direct intra-arterial blood pressure (radial artery) has been compared with indirect blood pressures using a regular sized adult cuff and a thigh cuff, with a mercury sphygmomanometer, in 24 hypertensive patients aged 62--84 years, and in 16 hypertensive patients aged 29--59 years. 2. The patients were studied because they were suspected of having a false elevation of their indirect blood pressure, since they had diastolic pressures over 100 mmHg, without hypertensive retinopathy, cardiac hypertrophy, or nephropathy. 3. Indirect diastolic pressure was falsely elevated by 30 mmHg or more in 12 out of 24 of the subjects over age 60, and in four of the 16 of those under age 60. Pseudohypertension (indirect diastolic greater than 100 mmHg, direct diastolic greater than 90 mmHg) was present in 12 subjects over age 60 and 5 under age 60. 4. Errors in indirect measurement of blood pressure are a serious problem, particularly in the elderly. Direct intra-arterial measurement may be useful in the management of hypertension.

1. In 20 subjects with uncomplicated essential hypertension, 10 of whom were on propranolol treatment, several blood samples were drawn simultaneously from the renal artery and vein after angiographic studies. In these samples we determined concentrations of noradrenaline, active renin, aldosterone and cortisol. 2. Renal blood flow was measured in all patients by Hippuran-clearance and xenon-washout. 3. Despite marked variations in the arteriovenous difference of noradrenaline, it was apparent in both groups that the kidney is able to release noradrenaline. 4. In the propranolol-treated group noradrenaline secretion with untreated hypertensive patients.

1. A total of 206 patients, elderly males with hypertension (diastolic blood pressure 95--110 mmHg) were followed for periods varying from 1 to 5 years, 107 patients with diastolic blood pressure less than 95 mmHg were followed over the same period, and 101 patients with diastolic blood pressure greater than or equal to 110 mmHg were also followed. 2. The mortality of each group and the effect of therapy for hypertension on mortality has been compared. 3. The incidence of myocardial infarct in the group treated with thiazide diuretics is greater than in the other groups. 4. It would appear unlikely that therapy will improve the prognosis in elderly people with mild hypertension.

1. In plasma samples from normal subjects and patients with untreated essential hypertension, the concentration of inactive renin (as measured after acidification) was on average 4-5 times higher than the concentration of active renin (as measured without acidification).2. Plasma angiotensin II concentration was correlated to active renin but not to inactive renin. 3. A hyperacute stimulation induced by infusion of saralasin resulted in a marked rise of active renin, whereas inactive renin remained unchanged. 4. An acute stimulation induced by frusemide and ambulation led to a considerable rise in active renin and a slight, but significant, rise of inactive renin. 5. Stimulation with oral thiazide over 5 days induced a seven-fold rise of active renin, with a doubling of inactive renin. Thiazide treatment for 3 months led to a four-fold rise of active renin and a three-fold rise of inactive renin. 6. There was no difference between the concentrations of inactive renin in systemic plasma, ipsilateral and contralateral renal venous plasma in 12 patients with renovascular hypertension, neither before nor after infusion of saralasin with the associated fall in blood pressure. 7. We conclude that the time constants pertinent to secretion or release of active and inactive renin in man are of different orders of magnitude.

1. The values for kallikrein, amylase and protein were determined in samples of saliva obtained from 220 girls aged 14--18 years. 2. The concentrations of protein and amylase and kallikrein activities (per ml of saliva) were considerably more variable in samples taken in the morning than those in the afternnon. 3. The median amylase activity was about two and a half times greater in the morning than that in the afternoon. No such differences were seen in the median values for protein or kallikrein. 4. Examination of the vlues for salivary kallikrein during the menstrual cycle showed that there was significantly greater activity during days 29--32 and 1--4 than during the rest of the cycle. This pattern was most marked in the morning values of kallikrein but not apparent either in the morning or in the afternoon values of protein or amylase.

1. Plasma renin activity, response to saralasin and exchangeable sodium have been measured in 43 patients with early renal disease. 2. Blood pressure was directly proportional to plasma renin activity. However, mean plasma renin activity was lower in patients with renal disease than in normal controls. 3. Blood pressure fell in response to saralasin infusion in proportion to the pre-infusion plasma renin activity. 4. Exchangeable sodium in hypertensive patients with renal disease did not exceed that in normotensive patients in contrast to earlier reports. Discrepancies may arise from the difficulty in interpreting measured exchangeable sodium in relation to body build.