Randomized double-blind placebo-controlled study of an angiotensin immunotherapeutic vaccine (PMD3117) in hypertensive subjects

2004 ◽  
Vol 107 (2) ◽  
pp. 167-173 ◽  
Author(s):  
Morris J. BROWN ◽  
John COLTART ◽  
Kulasiri GUNEWARDENA ◽  
James M. RITTER ◽  
Timothy R. AUTON ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Antibody Titre ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Primary Objective ◽  
Controlled Study ◽  
Double Blind ◽  
Show Evidence

Immunization against components of the renin–angiotensin system offers a potential alternative to daily medication in some patients with hypertension or heart failure. Our primary objective was to determine whether a sustained antibody titre to Ang I (angiotensin I) can be achieved in hypertensive patients. The secondary objective was to determine whether the antibodies block the renin system. Patients (n=27) with essential hypertension responsive to an ACEi (angiotensin-converting enzyme inhibitor) or ARB (angiotensin blocker) were randomly assigned to receive three or four injections of the Ang I vaccine PMD3117 or aluminium hydroxide (Alhydrogel™) over a 6 week period. Antibody titre was measured prior to each injection and every 30 days until disappearance. Indices of renin blockade were changes in renin and aldosterone (blood and urine) and a within-patient comparison of the pre- and post-vaccination rise in 24 h ambulatory blood pressure after 2 weeks of withdrawal of ACEi or ARB. The anti-(Ang I) antibody titre rose from the second injection in both regimes and peaked on day 64. Median half-life was 85 (95% CI, 44 and 153) days (where CI is confidence interval). Vaccination did not influence blood pressure, but significantly blunted the fall in plasma renin following withdrawal of ACEi or ARB. At 42 days after the first injection, aldosterone excretion was decreased by PMD3117 to 6 (95% CI, 1 and 31)% of values in patients receiving Alhydrogel™ (P=0.012). In patients with essential hypertension, PMD3117 generated a prolonged antibody response to Ang I. Biochemical measurements show evidence of blockade of the renin system, but higher titres will be required to achieve a decrease in blood pressure.

scholarly journals Effects of combined statin and ACE inhibitor therapy on endothelial function and blood pressure in essential hypertension - a randomised double-blind, placebo controlled crossover study

2019 ◽  
Vol 20 (3) ◽  
pp. 147032031986889 ◽  
Author(s):  
Piotr Ruszkowski ◽  
Anna Masajtis-Zagajewska ◽  
Michał Nowicki
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Angiotensin Converting Enzyme ◽  
Endothelial Function ◽  
Enzyme Inhibitor ◽  
Converting Enzyme ◽  
C Reactive Protein ◽  
Double Blind ◽  
Hypertensive Patients ◽  
Reactive Protein

Background: The aim of this study was to compare the influence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on endothelial function and blood pressure in patients with essential hypertension on long-term angiotensin-converting enzyme inhibitor therapy. Method: The study was designed as a prospective, double-blind, randomised, placebo controlled, crossover clinical trial. Twenty patients with essential hypertension were treated with an angiotensin-converting enzyme inhibitor; the control group included 10 healthy subjects. Hypertensive patients received in random order 80 mg of fluvastatin daily or placebo for 6 weeks. The following parameters were assessed at baseline and after each treatment period: serum lipids, flow-mediated vasodilation, activity of von Willebrand factor, concentration of vascular endothelial growth factor, C-reactive protein and 24-hour blood pressure profile. Results: Hypertensive patients did not differ from healthy subjects with respect to age, body mass and biochemical parameters, with the exception of C-reactive protein, which was higher in hypertensive patients ( P=0.02). After statin therapy, low-density lipoprotein cholesterol ( P<0.0001), C-reactive protein ( P=0.03), von Willebrand factor ( P=0.03) and vascular endothelial growth factor ( P<0.01) decreased and flow-mediated vasodilation improved ( P<0.001). Statins had no significant effect on blood pressure. Conclusions: Statins added to angiotensin-converting enzyme inhibitors may improve endothelial function and ameliorate inflammation independently of blood pressure.

Role of renin-angiotensin system in glucocorticoid hypertension in rats

1982 ◽  
Vol 243 (1) ◽  
pp. E48-E51 ◽  
Author(s):  
H. Suzuki ◽  
M. Handa ◽  
K. Kondo ◽  
T. Saruta
Keyword(s):  
Blood Pressure ◽  
Intravenous Injection ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Dependent Manner ◽  
Concurrent Administration ◽  
Angiotensin System ◽  
Renin Angiotensin

The role of the renin-angiotensin system in the regulation of the blood pressure of dexamethasone-treated rats (Dex) was evaluated using saralasin, an angiotensin II antagonist, and SQ 14225 (SQ) (d-3-mercapto-2-methylpropranoyl-1-proline), an angiotensin-converting enzyme inhibitor. During a 7-day period blood pressure rose 65 +/- 10 mmHg (P less than 0.001) in Dex with no significant changes in plasma renin activity. Concurrent administration of dexamethasone and SQ attenuated the elevation of blood pressure (P less than 0.05). In the conscious, freely moving state, intravenous injection of SQ (10, 30, 100 micrograms/kg) reduced blood pressure of DEX in a dose-dependent manner (P less than 0.05). Also, intravenous injection of saralasin (10 micrograms.kg-1 . min-1) reduced blood pressure significantly (P less than 0.01). Bilateral nephrectomy abolished the effects of saralasin and SQ on blood pressure in Dex. These results indicate that the elevation of blood pressure in DEX depends partially on the renin-angiotensin system.

Evaluation of the Effect of Timolol Alone and in Combination with Hydrochlorothiazide and Amiloride in the Treatment of Mild to Moderate Arterial Hypertension: A Double-Blind, Controlled Study

1976 ◽  
Vol 51 (s3) ◽  
pp. 529s-531s ◽  
Author(s):  
G. Muiesan ◽  
B. Magnani ◽  
E. Agabiti-Rosei ◽  
C. Alicandri ◽  
E. Ambrosioni ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Side Effects ◽  
Moderate Essential Hypertension ◽  
Fixed Dose ◽  
Controlled Study ◽  
Double Blind ◽  
Combination Tablet ◽  
Group A ◽  
Group B

1. The effects of timolol alone and in combination with a fixed dose of hydrochlorothiazide and amiloride have been studied in a double-blind, controlled study in fifty-four patients with mild to moderate essential hypertension. 2. After a 4 weeks placebo period patients were randomly assigned to enter groups receiving timolol alone (group A), hydrochlorothiazide + amiloride (group B) or timolol + hydrochlorothiazide + amiloride (group C). Each treatment was carried out for 6 weeks. 3. The use of timolol (10 mg), hydrochlorothiazide (25 mg) and amiloride (2·5 mg) in a combination tablet given twice daily gave better control of blood pressure in patients with mild to moderate essential hypertension than did equivalent dosages of timolol alone or of hydrochlorothiazide and amiloride. 4. Clinical and laboratory side effects were minimal.

Response of Chronic Renovascular Hypertension to Surgical Correction or Prolonged Blockade of the Renin–Angiotensin System by Two Inhibitors in the Rat

1980 ◽  
Vol 58 (1) ◽  
pp. 15-20 ◽  
Author(s):  
H. Thurston ◽  
R. F. Bing ◽  
E. S. Marks ◽  
J. D. Swales
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitor ◽  
Blood Pressure Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Chronic Hypertension ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Converting Enzyme Inhibitor

1. Removal of the renal artery constriction but not of the clipped kidney restored the blood pressure to normal levels in Goldblatt two-kidney rats with hypertension of more than 4 months' duration. 2. Despite the differences in blood pressure response, both surgical procedures lowered plasma renin concentration to normal or below normal values. 3. Administration of the oral converting enzyme inhibitor SQ 14 225 produced a marked fall in blood pressure in Goldblatt kidney rats with chronic hypertension. However, a prolonged infusion of the angiotensin II antagonist saralasin was quite ineffective. The difference in response to the two inhibitors may have been due to bradykinin potentiation by the converting enzyme inhibitor. 4. Although plasma renin is often elevated in Goldblatt two-kidney rats with hypertension of more than 4 months' duration, the renin-angiotensin system plays no role in the maintenance of blood pressure at this stage.

A Controlled Study on the Anti-Hypertensive Effect of a new β-Adrenoreceptor-Blocking Drug, Metoprolol, in Combination with Chlorthalidone

1976 ◽  
Vol 51 (s3) ◽  
pp. 521s-523s ◽  
Author(s):  
A. Jäättelä ◽  
K. Pyörälä
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Side Effects ◽  
Moderate Hypertension ◽  
Moderate Essential Hypertension ◽  
Controlled Study ◽  
Blocking Drug ◽  
Double Blind ◽  
Basic Treatment

1. A double-blind cross-over evaluation of the anti-hypertensive effect of metoprolol vs placebo was carried out in a series of twenty-three patients with mild or moderate essential hypertension who were receiving 25 mg of chlorthalidone daily as their basic treatment. An individually determined dose of metoprolol (75–300 mg) was used. 2. Metoprolol, as compared with placebo, produced a statistically significant reduction of blood pressure, both in supine and standing positions. 3. During the double-blind cross-over study mild side effects were more common at the beginning of metoprolol/chlorthalidone treatment than during placebo/chlorthalidone, but these tended to diminish or disappear with time. 4. Metoprolol in combination with chlorthalidone appears to be an effective and well-tolerated treatment for mild and moderate hypertension in patients not responding to chlorthalidone alone.

Effects of Angiotensin II on Insulin Sensitivity: A Placebo-Controlled Study

1993 ◽  
Vol 85 (4) ◽  
pp. 431-436 ◽  
Author(s):  
A. D. Morris ◽  
J. R. Petrie ◽  
J. Anderson ◽  
J. M. C. Connell ◽  
R. Donnelly
Keyword(s):  
Blood Pressure ◽  
Insulin Sensitivity ◽  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Serum Insulin ◽  
Whole Body ◽  
Controlled Study ◽  
High Dose ◽  
Double Blind ◽  
Plasma Angiotensin

1. There is evidence that hyperinsulinaemia increases the aldosterone response to angiotensin II, and that angiotensin-converting enzyme inhibitor drugs enhance peripheral glucose utilization, but the direct effects of angiotensin II on insulin sensitivity have not been reported previously. 2. In a randomized, double-blind, placebo-controlled, cross-over study, 12 healthy male subjects attended on 3 study days for the evaluation of the effects of a subpressor (1 ng min−1 kg−1) and pressor (5 ng min−1 kg−1) infusion of angiotensin II on whole-body insulin sensitivity using the euglycaemic hyperinsulin-aemic clamp. Frequent measurements of blood pressure and heart rate were recorded and blood samples were collected for determination of serum insulin, C-peptide and K+ concentration, plasma renin activity and plasma angiotensin II concentration. 3. Plasma angiotensin II concentrations (means +SD) were 11+5 pg/ml after placebo, and 27+9 and 125+28 pg/ml after low and high dose angiotensin II, respectively. The higher dose of angiotensin II was associated with significant increases in blood pressure (e.g. 13 mmHg systolic blood pressure at 150 min) and serum aldosterone concentration. Whole-body insulin sensitivity was 10.5 + 2 mg of glucose min−1 kg−1 after placebo, and 10.5 +2.2 and 10.9+3.4 mg of glucose min−1 kg−1 after low and high dose angiotensin II (not significant). 4. Angiotensin II had no effect on hyperinsulinaemia-induced reductions in serum potassium and triacyl-glycerol concentrations. 5. Thus, acute infusion of angiotensin II for 3 h, with or without an increase in blood pressure, has no effect on whole-body insulin sensitivity.

Angiotensin Activates Sympathetic Reflexes in the Anaesthetized Cat

1980 ◽  
Vol 59 (s6) ◽  
pp. 287s-289s ◽  
Author(s):  
D. P. Clough ◽  
R. Hatton ◽  
J. Conway ◽  
S. A. Adigun
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renin Activity ◽  
Converting Enzyme ◽  
Reduced Pressure ◽  
Converting Enzyme Inhibitor ◽  
Sympathetic Reflexes

1. Lower-body subatmospheric pressure has been used to stimulate sympathetic reflexes in anaesthetized cats and the effects of an angiotensin converting enzyme inhibitor and [Sar1, Ala8]angiotensin II have been investigated on this reflex. 2. At the prevailing level of renin activity (2.9-3.2 ng of angiotensin I h−1 ml−1) the converting enzyme inhibitor had no effect on blood pressure yet it potentiated the initial fall in blood pressure caused by the reduced pressure and it impaired its recovery. After 10 min, therefore, blood pressure was still reduced after converting enzyme inhibitor treatment whereas in control experiments full recovery occurred within 30 s. 3. When converting enzyme inhibitor was given 75 s after the start of a 10 min period of reduced pressure, at a time when plasma renin activity had not been increased, it caused a greater and more sustained fall in pressure than it caused when administered alone. The angiotensin II antagonist, [Sar1,Ala8]angiotensin II, produced similar effects. 4. These findings suggest that the renin-angiotensin system interacts with the sympathetic nervous system to maintain systemic arterial pressure.

A 24-Week Dose-Titration Study of the Angiotensin-Converting Enzyme Inhibitor Imidapril in the Treatment of Mild-to-Moderate Essential Hypertension in the Elderly

2001 ◽  
Vol 29 (2) ◽  
pp. 100-107 ◽  
Author(s):  
I Dews ◽  
M VandenBurg
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Elderly Patients ◽  
Enzyme Inhibitor ◽  
The Elderly ◽  
Moderate Essential Hypertension ◽  
Dose Titration ◽  
Double Blind Study ◽  
Double Blind ◽  
Intent To Treat

This multicentre, randomized, double-blind study compared the anti-hypertensive efficacy and safety of oral once-daily imidapril 5–20 mg and hydrochlorothiazide 12.5–50 mg in elderly patients with mild-to-moderate essential hypertension. After 24 weeks of treatment, there was a significant reduction in mean sitting diastolic blood pressure from 102.5 mmHg to 87.2 mmHg in the imidapril group ( n = 226) and from 102.7 mmHg to 87.4 mmHg in the hydrochlorothiazide group ( n = 123) (intent-to-treat population). There were corresponding reductions in sitting systolic blood pressure and standing blood pressure. At least one adverse event was reported by 46% of patients in the imidapril group and 53% of patients in the hydrochlorothiazide group. Imidapril 5–20 mg is as effective and well tolerated as hydrochlorothiazide in the treatment of mild-to-moderate hypertension in elderly patients.

Blood Pressure Response of Nephrectomized Hypertensive Rats to Converting Enzyme Inhibition: Evidence for Persistent Vascular Renin Activity

1977 ◽  
Vol 52 (3) ◽  
pp. 299-304 ◽  
Author(s):  
H. Thurston ◽  
J. D. Swales
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renin Activity ◽  
Converting Enzyme ◽  
Bilateral Nephrectomy ◽  
Hypertensive Rats ◽  
Angiotensin System

1. Blood pressure and plasma renin activity were studied after bilateral nephrectomy in groups of rats with hypertension caused by unilateral renal ischaemia with the opposite kidney left intact. 2. Although blood pressure showed only a small fall in the first hour after bilateral nephrectomy, plasma renin activity fell rapidly with a half-life of 10 min. 3. Infusion of converting enzyme inhibitor (SQ20881) produced a 26·1% fall in blood pressure 1 h after nephrectomy, 24·0% at 2 h and 4·6% at 6 h. 4. An angiotensin antagonist (Sar1-Ala8-angiotensin II) was infused into hypertensive rats 1 h after nephrectomy; this blocked the vasodepressor action of the converting enzyme inhibitor, indicating that the fall in blood pressure produced by the inhibitor was due to its action upon the renin-angiotensin system. 5. The renin—angiotensin system maintains blood pressure in this model even after plasma renin has fallen to insignificant levels. This supports the view that vascular renin activity has a longer half-life than circulating renin and is important in the control of blood pressure.

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