Effects of changes in angiotensin converting enzyme activity on renin release: pretreatment with dexamethasone enhances a plasma renin activity response to captopril in normal subjects.

Healthy adults were given captopril (25 mg and 75 mg) po with or without dexamethasone (DXM) pretreatment (1 mg po 2 h before and simultaneously with the captopril). We determined the serum potassium and sodium concentrations, plasma prostaglandin E2 level, PRA, serum angiotensin converting enzyme (ACE) activity, and aldosterone level from 20 min before to 120 min after administration of captopril. DXM pretreatment stimulated the PRA response to captopril. This stimulation was suppressed by indomethacin. However, the administration of DXM did not induce a consistent rise in the prostaglandin E2 level. The administration of DXM induced a significant rise in the potassium concentration, but since simultaneous administration of indomethacin with captopril induced the suppression of PRA without affecting the potassium level, the PRA increase in response to captopril with DXM was not caused directly by the potassium increase. There were no significant differences in the PRA increase between 25 mg captopril and 75 mg captopril, or between DXM-25 mg captopril and DXM-75 mg captopril, though the inhibitions of ACE activity by captopril differed according to dose. The PRA increases, but not the captopril-induced inhibition of ACE activity, were significantly different between captopril alone and captopril with DXM pretreatment at either dose of captopril. Thus, the inhibition of ACE activity perhaps allows PRA to increase in response to captopril. These results suggest that the DXM stimulation of PRA may have been dependent on the inhibition of ACE activity by captopril.     

Effects of converting enzyme inhibition on blood pressure, plasma renin activity (PRA) and plasma aldosterone in hypertensive diabetics compared to patients with essential hypertension

Hypertension with diabetes mellitus has been associated with suppression of the renin-angiotensin-aldosterone system. We have studied the effects of the converting enzyme inhibitor, captopril, on blood pressure, plasma renin activity (PRA) and plasma aldosterone in 10 stable hypertensive diabetic subjects and 10 age-matched patients with essential hypertension. There was no clinical evidence of complication in the diabetic subjects and their diabetic treatment remained unchanged throughout the study. Mean captopril doses used were similar in both groups. In the diabetics and the essential hypertensives, treatment resulted in a significant and similar decrease in blood pressure. Pre-treatment basal and stimulated PRA and the change of PRA with captopril were also similar. Pre-treatment stimulated plasma aldosterone and the response of aldosterone to postural stress was significantly lower in the diabetic group, suggesting an impaired adrenal responsiveness to stress. Despite this, our findings indicate that the hypotensive action of captopril is at least as effective in hypertension associated with otherwise uncomplicated diabetes mellitus as in essential hypertension.     

Serum angiotensin I converting enzyme activity in patients with hyperthyroidism and hypothyroidism: relation to renin and aldosterone

In order to ascertain whether angiotensin I converting enzyme (ACE) activity might be regulated by thyroid hormone, serum ACE activity was measured in a variety of thyroid states, including hyperthyroid and hypothyroid subjects. In addition, the correlation of serum ACE activity to plasma renin activity (PRA) and plasma aldosterone concentration (PAC) was evaluated in these patients. In hyperthyroid patients, the mean (+/- SD) serum ACE activity was 32.7 +/- 6.7 U/ml (n = 30), which was significantly higher than that in hypothyroid patients (20.4 +/- 4.3 U/ml, n = 7, p less than 0.001) and in normal subjects (22.5 +/- 3.4 U/ml, n = 51, p less than 0.001). No significant difference in serum ACE activity was found between the hypothyroid patients and normal subjects. There was a significant positive correlation between serum ACE activity and PRA (r = 0.524, n = 30, p less than 0.01) and also between serum ACE activity and PAC (r = 0.473, n = 30, p less than 0.01) in the patients with hyperthyroidism. By contrast, no significant relationship was observed between serum ACE activity and thyroid hormones (r = 0.115, for T3; r = 0.143, for T4) in hyperthyroid patients. Treatment with furosemide (1 mg/kg i.v.) and upright posture (2h) significantly increased PRA, PAC and serum ACE activity in both hyperthyroid patients and normal subjects, but not in hypothyroid patients. There was a significant positive correlation between changes in serum ACE activity and in PRA (r = 0.418, n = 23, p less than 0.05) in response to the treatment in hyperthyroid patients, while no significant relationship was observed between them in either hypothyroid patients (r = 0.216, n = 6, p less than 0.10) or normal subjects (r = 0.620, n = 10, 0.05 less than p less than 0.01). In one patient with hyperthyroidism, administration of propranolol decreased PRA from 3.4 to 2.3 ng/ml/h, corresponding to an apparent decrease in serum ACE activity from 38.7 to 29.6 U/ml. From these results, it is suggested that serum ACE activity in the hyperthyroid state is modulated by the renin-angiotensin system rather than by thyroid hormone.     

Effect of inhibition of converting enzyme by captopril on arterial pressure, renin and aldosterone in essential hypertension

The response of arterial blood pressure, plasma renin activity (PRA) and plasma (PA) or urinary aldosterone (UA) concentrations to the administration of captopril, was studied in patients with established essential hypertension. Captopril was effective in lowering significantly the blood pressure (189.4/111.2 +/- 23.9/9.7 to 163.4/98.1 +/- 20.7/8.6 mmHg. mean +/- SD, p less than 0.01/0.001). Normal arterial blood pressure values (140.4/86.5 +/- 20.7/10.8 mmHg, were achieved by the addition of hydrochlorothiazide. Captopril administration was followed by a decrease in PA and in UA and an increase in PRA, suggesting the inhibition of angiotensin II formation. Captopril attenuated hypokalemia and hyperaldosteronism produced by the simultaneous administration of hydrochlorothiazide.     

Fluctuations in the plasma angiotensin I converting enzyme activity during long-term treatment with captopril

Eight hypertensive patients on chronic captopril treatment were studied: blood pressure, plasma converting enzyme activity (pCEA) and various components of plasma renin-angiotensin-aldosterone system were measured repeatedly, immediately before and up to 7 hours after the usual morning dose of captopril in 5 patients, or a matching placebo in 3 patients. In the patients, receiving a placebo no significant changes were observed over a 7 hour period in pCEA, plasma rénin activity (PRA), plasma angiotensin II (ANG II) plasma aldosterone (PAC) and blood pressure. In patients receive captopril (200 mg) pCEA rapidly decreased, reaching after 2 hours a minimum, corresponding to nearly 20 per cent of its reference value. Thereafter pCEA increased and after 7 hours remained only slightly depressed. Within the first hour after captopril intake a small but significant decrease of ANG II and PAC was observed, while PRA and blood pressure remained unchanged throughout the study period. A continuous low pCEA level is therefore not necessary to achieve a sustained blood pressure lowering effect during chronic captopril treatment.     

Negative association between plasma aldosterone concentration/plasma renin activity and morning blood pressure surge in never-treated hypertensive patients

Morning blood pressure (BP) surge (MS) has been known to be a predictor of cardiovascular events. Currently, few studies have evaluated the underlying mechanism underlying MS, which may include neurohormonal factors and the renin–angiotensin–aldosterone system (RAAS). This study aimed to examine plasma aldosterone concentration (PAC) and plasma renin activity (PRA) and BP parameters with or without MS in never-treated subjects with essential hypertension. This cross-sectional study included a total of 261 patients (mean age: 48.8 years; 60.5% male) with never-treated essential hypertension who were registered in a working group at The Catholic University of Korea. The patients were divided into the MS group, which was defined as having the highest quartile of morning BP increase from sleep (>31?mmHg; n?=?66) and the non-MS group (≤31?mmHg; n?=?195). We collected 24-h ambulatory BP, pulse wave velocity, ankle brachial index, PAC and PRA from all patients. The measured PAC and PRA were lower in the MS group than in the non-MS group (PAC: 9.0?±?5.4?ng/dl versus 12.2?±?8.7?ng/dl, p?p?=?0.002). The MS group had greater variations in daytime, nighttime and 24-h systolic blood pressure (SBPs) than the non-MS group (24-h SBP: 15.6?±?4.4?mm Hg for the non-MS group and 18.9?±?4.9?mmHg for the MS group; p?相似文献   

A dynamic study of plasma renin activity and aldosterone concentration in normal and hypertensive subjects

Variations of plasma renin activity (PRA) and plasma aldosterone concentration have been studied after a water load with a 2-hour period of recumbency followed by furosemide infusion in five normal subjects and seven hypertensive patients. It has been found following furosemide infusion that there is a lag of 15 min between the increase in PRA and that of aldosterone. PRA and aldosterone levels are still elevated when diuresis and natriuresis have returned close to normal. Patients with essential hypertension behave like normal subjects during this dynamic test except for one patient with abnormally low PRA and low normal levels of plasma aldosterone. The two patients with primary aldosteronism were able to modify their aldosterone concentration as normal subjects did, but at all times their levels remained higher. Plasma aldosterone concentration as a diagnostic screening test should be performed in the upright position.     

Correlations between plasma renin activity, angiotensin II, and aldosterone.

To obtain more information about the relationships of the components of the renin-angiotensin-aldosterone system, we measured plasma renin activity (PRA) and the concentrations of plasma angiotensin II (AII) and aldosterone (PA) in 36 healthy 19-22-yr-old students, both after a night's bed rest and after 2 h of ambulation. The correlations of these parameters were calculated. PRA, AII, and PA were determined by RIAs. The values of AII after rest correlated positively both with PRA (r = 0.80; P less than 0.001) and with PA (r = 0.51; P less than 0.01). AII also showed a good correlation with PRA (r = 0.77; P less than 0.001) and with PA (r = 0.67; P less than 0.01) after ambulation. The latter correlation was higher than that after rest. Positive correlations were also found between the increases in PRA and AII and between AII and PA. Further, a multiple regression analysis was carried out to calculate the regression equations for these parameters. The results support the view that PRA and AII parallel each other in normal physiological circumstances. They also seem to indicate that AII has an important role in the basal as well as in the posture-stimulated secretion of aldosterone in normal man.     

Novel mass spectrometric methods for evaluation of plasma angiotensin converting enzyme 1 and renin activity

This article demonstrates the applicability of quantitative proteomics to assays of proteolytic enzyme activity. A novel assay was developed for measurement of renin and angiotensin-converting enzyme (ACE) activity in plasma. The method was validated in animal models associated with alterations of the renin angiotensin system (RAS). Using surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) with a ProteinChip Array technology, plasma renin and ACE1 could be measured in <0.5 microL of plasma. Plasma is incubated with peptide substrates for renin and ACE, tetradecapeptide (TDP), and angiotensin I (Ang I), respectively. The reactions mixtures are spotted onto the ProteinChip WCX2 and detected using SELDI-TOF-MS. Peak height or area under curve for TDP, Ang I, and angiotensin II (Ang II) peaks are measured. There was a linear relationship between disappearance of substrate and appearance of products for both renin and ACE (R2=0.95 to 0.98). ACE1 activity was blocked with chelating agents (EDTA and 1,10 phenanthrolene), indicating action of a metalloprotease. The ACE1 inhibitor, captopril, selectively blocked ACE1. Renin activity was specifically blocked with renin inhibitor and was not affected by phenanthrolene or captopril. Animal models tested were Ang AT1a receptor-deficient and streptozotocin (STZ) diabetic mice. Plasma renin activity was increased >2-fold in AT1a(-/-) as compared with AT1a(+/+). In STZ diabetic mice, ACE1 was increased 2-fold as compared with controls. The advantage of the method is that it is tagless, does not require additional purification steps, and is extremely sensitive. The approach can be multiplexed and used for identification of novel substrates/inhibitors of the RAS.     

Acute effect of atenolol on hemodynamic, plasma renin activity and plasma aldosterone concentration in the once daily oral administration

A new beta-blocking agent, atenolol was studied on the supposition that it was a beta-blocker without any action on central nervous system. Atenolol was orally given to 10 patients with essential hypertension once a day and changes in various parameters were observed through 24 hours. As the results, hypotensive effect was accompanied by marked reduction of heart rate, systemic vascular resistance, plasma renin activity and blood aldosterone level over 24 hours. It was a decrease in systemic vascular resistance that showed best correlation with hypotensive effect.     

Familial elevation of serum angiotensin converting enzyme activity

A clustering of high levels of serum angiotensin converting enzyme (S-ACE) was found in an Italian family. The elevation affected five subjects, two of whom were completely healthy and free from known causes of S-ACE increase. The values of S-ACE in hyperACEmic subjects exceeded the values found in normal relatives severalfold. HyperACEmia seemed to be inherited as an autosomal dominant trait. Immunogenetic studies were performed, but we did not find a genetic marker for this condition. The S-ACE activity was inhibited in vitro by edetic acid (EDTA) and SQ 14,225 (captopril). The S-ACE activity was also determined after 1:8 dilution and dialysis against saline of sera. From these experiments we deduced that Lieberman's intrinsic ACE inhibitor was lacking in the hyperACEmic sera. In the presence of remarkable S-ACE increase, a congenital elevation of S-ACE should be considered and it would be useful to perform a familial investigation.     

Effects of beta-adrenergic blocking agents on the blood pressure, plasma renin activity and hemodynamics of hypertensive patients.

Changes in blood pressure, plasma renin activity, and hemodynamic components were studied in 23 patients with essential hypertension treated with oral pindolol or propranolol. These beta-adrenergic blocking agents effectively lowered the blood pressure in the majority of the patients. Although plasma renin activity was not significantly changed, the higher was the pretreatment level, the more it tended to be decreased. Systemic vascular resistence was significantly decreased, while changes in cardiac index and circulating blood volume were variable. Pindolol showed less effect in reducing the heart rate than propranolol. The antihypertensive effect of these drugs had no correlation with the change in plasma renin activity or in any one of hemodynamic components.     

Active and inactive renin after a single dose of captopril in hypertensive patients

In 25 hypertensive patients (15 with renal artery stenosis and 10 with essential hypertension), captopril, in a single 12.5 mg dose, caused a prompt decrease in arterial pressure without changing the heart rate. Plasma active and trypsin-activated renin significantly increased, whereas inactive renin and plasma aldosterone decreased. The plasma active/ inactive renin ratio was also increased, suggesting that captopril, together with a release of active renin, may induce an in vivo activation of inactive renin.No correlations were found between blood pressure changes and both pretreatment and captopril-induced variations of active, inactive and trypsin-activated renin or the active/inactive ratio. However, the percent decrease in mean arterial pressure was significantly related to the increase in the active/inactive renin ratio in a group of patients whose blood pressure was brought to normal (r = ?0.78; p < 0.001). This finding suggests the possibility that vasodilating substances, in addition to inhibiting angiotensin II formation, might play some role both in exerting a full effect of captopril on blood pressure and in triggering the in vivo mechanisms of inactive renin activation.     

The acute effects of the new angiotensin I-converting enzyme inhibitor, enalapril maleate, on blood pressure, plasma renin, aldosterone and kinins in hypertensive patients

The acute antihypertensive effect of a new long-acting oral angiotensin I-converting enzyme (ACE) inhibitor, enalapril maleate, was assessed in 20 hypertensive patients, of whom 14 had essential hypertension, 4 had renovascular hypertension, one had hypertension associated with chronic renal failure, and one had primary aldosteronism. Enalapril maleate significantly lowered the blood pressure in either low-renin or normal- and high-renin hypertensives. There was a significant correlation for all patients as a group between the pretreatment levels of serum ACE activity and the reduction in mean blood pressure (r = -0.454, p less than 0.05, n = 20) 2 h after drug administration. The serum ACE activity decreased maximally 3 to 4 hours after drug administration and did not return to baseline levels within 24 h. There was a significant correlation between the reduction in mean blood pressure and changes in ACE activity 90 min and 2 h after drug administration, respectively, for all patients as a group (r = 0.495, p less than 0.05, n = 20, at 90 min; r = 0.508, p less than 0.05, n = 20, at 2 h). The plasma renin activity (PRA) significantly increased in normal- and high-renin hypertensives but not in low-renin hypertensives. There was a close correlation between the reduction in mean blood pressure and the PRA 8 h after drug administration in normal- and high-renin patients (r = -0.623, p less than 0.05, n = 13), while no such relationship was observed in low-renin patients. The plasma aldosterone concentration (PAC) significantly decreased within 3 h, the lowest values occurring at 8 h after drug administration, and it returned to baseline levels within 24 h in all patients. No relationship was found between the reduction in mean blood pressure and changes in PAC after drug administration in either low-renin or normal- and high-renin hypertensives. The plasma bradykinin concentration (PBC) increased within 1 h, the highest values occurring at 3 h after drug administration, and returned to baseline levels within 24 h in low-renin hypertensives, while the PBC was significantly increased at 4 h and had not returned to baseline levels within 24 h in normal- and high-renin hypertensives. There was a significant correlation between percentage changes in mean blood pressure and those in PBC 90 min after drug administration in normal- and high-renin hypertensives (r = -0.556, p less than 0.05, n = 13), while no relationship was observed between them in low-renin hypertensives.(ABSTRACT TRUNCATED AT 400 WORDS)