Plasma Renin Activity and Angiotensin Pressor Dose in Hypertension: Correlation and Diagnostic Implications

Data obtained from 65 hypertensive patients showed a clear-cut positive correlation between peripheral plasma renin activity and the pressor response to exogenous angiotensin II (r =+0.75). For the various causes of hypertension, the mean values of plasma renin concentration were found to correspond closely to the mean values of the angiotensin pressor dose. In individual cases, however, the pressor dose of angiotensin was not found to be a reliable gauge of peripheral venous renin activity.It was impossible to establish a causal diagnosis from the results of the angiotensin infusion test or the renin level in peripheral blood under normal conditions. If, however, determinations are carried out on the renal venous effluent with sodium restriction and with the patient in the upright position the renin level is very valuable both in the diagnosis of renovascular hypertension and in predicting the probable outcome of surgical treatment.     

The Angiotensin Infusion Test and Peripheral Venous Renin Activity

Forty hypertensive patients were studied to examine the assumption that the angiotensin pressor dose reflects endogenous renin activity. Peripheral renin activity was assayed by the method of Boucher et al.⁴ Sensitivity to the infusion of synthetic angiotensin II was determined as suggested by Kaplan and Silah.¹Sixteen patients with essential hypertension with normal renal angiography required 3.8 ng. angiotensin/kg./min. to raise the diastolic pressure 20 mm. Hg. All but one were sensitive to angiotensin infusion of less than 5 ng./kg./min. Renin activity was normal in all except in one sensitive subject. Angiotensin infusion response and mean renin activity in 13 patients with essential hypertension with abnormal renal angiography were similar to that of the first group. The pressor dose in 11 renovascular hypertensives was 9.8 ng./kg./min. All but three had elevated plasma renin activity.Our results suggest that: (1) the angiotensin infusion test is suitable for differentiating patients with true renovascular hypertension from those with essential hypertension with or without associated renal artery disease; (2) the angiotensin pressor dose correlates with the level of peripheral venous renin activity (p < 0.01).     

Plasma Renin Levels and Vascular Complications in Hypertension

Plasma renin levels, measured in 39 untreated patients in 1967, under conditions of sodium loading and sodium depletion have been related to the incidence of stroke and myocardial infarction. Renin levels were not significantly different in patients with or without vascular complications. Out of 13 patients with persistently low renin levels 6 had suffered either a stroke or a myocardial infarction and 7 had not. Plasma renin levels were also measured in 116 treated hypertensive patients. There was no relation between plasma renin level and vascular complications. It is concluded that levels of plasma renin are not a reliable index of the probability of hypertensive patients suffering a stroke or myocardial infarction.     

β-Blockers and Plasma Renin Activity in Hypertension

Long-term treatment with propranolol was shown to produce a sustained suppression of the renin-aldosterone system in hypertensive patients, despite concurrent diuretic treatment. However, the antihypertensive effect of this treatment correlated poorly with its effects on plasma renin activity and urinary aldosterone excretion. When prindolol, another β-adrenergic blocking drug, was substituted for propranolol, blood pressure control was retained, but there was a prompt rise in plasma renin activity, which was not attributable to changes in electrolyte balance. These observations suggest that the antihypertensive action of propranolol and other β-blockers does not result from their effects on plasma renin activity.     

肾素-血管紧张素系统与子痫前期关系的研究进展

子痫前期是妊娠期特有的疾病。目前子痫前期的病因和发病机制尚未完全阐明,在其发生和发展过程中涉及到多种因素, 其中肾素- 血管紧张素系统（RAS）失调是子痫前期重要发病原因之一,参与子痫前期的病理生理学变化。本文就系统循环和子宫 胎盘RAS 各组分,尤其胃促胰酶(Chymase)和AT1 受体自身抗体（AT1-AA）,在子痫前期的发生和发展中的变化和作用进行阐 述。     

Significance of High Plasma Renin Activity in Patients on Maintenance Haemodialysis Therapy

Blood pressure and plasma renin activity were remeasured after an interval of 8 to 17 months in 16 patients on maintenance haemodialysis previously found to have high renin activity. Continuing intermittent haemodialysis changed the plasma renin activity and blood pressure but no consistent pattern was seen. This confirmed our previous finding that adequate dialysis can control blood pressure in the presence of high renin activity. We therefore conclude that bilateral nephrectomy should be approached with renewed caution.     

Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay

In response to injury, blood coagulation is activated and results in generation of the clotting protease, thrombin. Thrombin cleaves fibrinogen to fibrin which forms an insoluble clot that stops hemorrhage. Factor V (FV) in its activated form, FVa, is a critical cofactor for the protease FXa and accelerator of thrombin generation during fibrin clot formation as part of prothrombinase ^{1, 2}. Manual FV assays have been described ^{3, 4}, but they are time consuming and subjective. Automated FV assays have been reported ^5-7, but the analyzer and reagents are expensive and generally provide only the clot time, not the rate and extent of fibrin formation. The microplate platform is preferred for measuring enzyme-catalyzed events because of convenience, time, cost, small volume, continuous monitoring, and high-throughput ^{8, 9}. Microplate assays have been reported for clot lysis ¹⁰, platelet aggregation ¹¹, and coagulation Factors ¹², but not for FV activity in human plasma. The goal of the method was to develop a microplate assay that measures FV activity during fibrin formation in human plasma.This novel microplate method outlines a simple, inexpensive, and rapid assay of FV activity in human plasma. The assay utilizes a kinetic microplate reader to monitor the absorbance change at 405nm during fibrin formation in human plasma (Figure 1) ¹³. The assay accurately measures the time, initial rate, and extent of fibrin clot formation. It requires only μl quantities of plasma, is complete in 6 min, has high-throughput, is sensitive to 24-80pM FV, and measures the amount of unintentionally activated (1-stage activity) and thrombin-activated FV (2-stage activity) to obtain a complete assessment of its total functional activity (2-stage activity - 1-stage activity).Disseminated intravascular coagulation (DIC) is an acquired coagulopathy that most often develops from pre-existing infections ¹⁴. DIC is associated with a poor prognosis and increases mortality above the pre-existing pathology ¹⁵. The assay was used to show that in 9 patients with DIC, the FV 1-stage, 2-stage, and total activities were decreased, on average, by 54%, 44%, and 42%, respectively, compared with normal pooled human reference plasma (NHP).The FV microplate assay is easily adaptable to measure the activity of any coagulation factor. This assay will increase our understanding of FV biochemistry through a more accurate and complete measurement of its activity in research and clinical settings. This information will positively impact healthcare environments through earlier diagnosis and development of more effective treatments for coagulation disorders, such as DIC.     

Plasma Renin Activity and Blood Pressure in 89 Patients Receiving Maintenance Haemodialysis Therapy

Blood pressure, plasma renin activity, plasma sodium concentration, plasma potassium concentration, dietary sodium intake, and duration of dialysis have been measured under standard conditions in 89 patients on maintenance haemodialysis. No significant relation was found between plasma renin activity and blood pressure. Statistically significant correlations were found between plasma renin activity and plasma sodium concentration and between plasma renin activity and dietary sodium intake.Only one patient was found to have uncontrollable hypertension associated with a markedly raised plasma renin activity. Reasons are given for not performing bilateral nephrectomy in this patient. We believe the low incidence of uncontrollable hypertension and hyperreninaemia in our patients to be due to their slow introduction to haemodialysis, thus preventing violent swings in body weight, blood pressure, and renin secretion.Although plasma renin activity did fall with duration of dialysis, all 15 patients who have been on maintenance dialysis for longer than five years have normal levels.     

Hypertension,Increased Aldosterone Secretion and Low Plasma Renin Activity Relieved by Dexamethasone

A father and son are described with a condition characterized by benign hypertension, potassium deficiency, increased aldosterone secretion rate (ASR), raised plasma volume and suppressed plasma renin activity (PRA). There were intermittent elevations of urine 17-ketosteroids and 17-hydroxycorticoids (17-OHCS) but no increase in urine THS, normal circadian rhythm of plasma 17-OHCS, and normal urine 17-OHCS response to dexamethasone and intravenous ACTH. Plasma ACTH and corticosterone secretion were not elevated. Pregnanetriol excretion was normal but urine pregnanediol was increased. At operation on the father no adrenal tumour was found; the excised left adrenal weighed 7 g. and showed nodular cortical hyperplasia; juxtaglomerular cells showed only occasional granules. Following operation hypertension persisted and ASR was half the preoperative value. All abnormalities in father and son were relieved by dexamethasone (DM) 2 mg. daily. The condition recurred following cessation of DM but was relieved by a second course of treatment. No such response to DM was seen in a normal subject or in a patient with Conn''s syndrome. For a number of reasons it is suggested that patients with hypertension, increased ASR and low PRA be given a trial of dexamethasone treatment before undergoing adrenal surgery.     

Measurement of Human Daily Physical Activity

Objectives: To validate a new device, Intelligent Device for Energy Expenditure and Activity (IDEEA), for the measurement of duration, frequency, and intensity of various types of human physical activity (PA). Research Methods and Procedures: The ability of IDEEA to identify and quantify 32 types of PA, including the most common daily exercise and nonexercise PA, was tested in 76 subjects: Subjects included males (N = 33) and females (N = 43) ranging in age from 13 to 72 years with a mean body mass index (BMI) of 24.7 kg/m² (range: 18.4 to 41.0) [43 females: 13 to 72 years old and BMI 18.4 to ～41.0 kg/m² (mean = 24.7 kg/m² ); 33 males: 15 to ～72 years old and BMI 21.0 to ～38.4 kg/m² (mean = 25.9 kg/m²)]. Postures, limb movements, and jumping were tested using a timed protocol of specific activities. Walking and running were tested using a 60‐meter track, on which subjects walked and ran at 6 self‐selected speeds. Stair climbing and descending were tested by timing subjects who climbed and descended a flight of stairs at two different speeds. Results: Correct identification rates averaged 98.9% for posture and limb movement type and 98.5% for gait type. Pooled correlation between predicted and actual speeds of walking and running was high (r = 0.986, p ≤ 0.0001). Discussion: IDEEA accurately measured duration, frequency, type, and intensity of a variety of daily PAs.     

Measurement of Arginine Carboxypeptidase-Generating Activity of Adult Plasma

Arginine carboxypeptidase (CPR) is a novel carboxypeptidase which was first described by Campbell and Okada. CPR is generated from a stable precursor of CPR (proCPR) during coagulation or under other circumstances and is promptly inactivated at 37 C. Therefore, it is not easy to determine CPR in blood samples. Since proCPR can be separated from the other basic carboxypeptidase (carboxypeptidase N; CPN) by passing plasma through DEAE gel, we have established a method to determine the amount of proCPR after converting it to active CPR by trypsin treatment. We first separated the proCPR from CPN using a filter cup tube (FC tube) packed with DEAE Sephadex, and measured activity after conversion of the enzyme to its active form using trypsin. With this method, no significant decrease in proCPR was noted in the plasma of patients including those with rheumatoid arthritis (RA), although CPR activity in fresh sera has been reported to be decreased. This discrepancy suggests that proCPR is not depleted in most patient sera, but that the level of activity of the enzyme which converts proCPR into active CPR may be compromised in RA patients.