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PubMed1987

Inhibition of angiotensin-converting enzyme by perindopril diacid in canine oleic acid pulmonary edema.

To test the hypothesis that angiotensin II could be a mediator of acute lung injury, we studied the effects of perindopril diacid, a new angiotensin-converting enzyme inhibitor, on hemodynamics, blood gases, lung mechanics, and extravascular lung water (EVLW). Twenty-four dogs were anesthetized, paralyzed and ventilated with a fraction of inspired oxygen of 0.4 in which pulmonary edema was induced by 0.1 ml/kg iv oleic acid. Perindopril diacid (1 mg/kg) was administered iv either before (eight dogs) or 100 min after (eight dogs) oleic acid injection. In the control group (eight dogs) not treated with perindopril diacid, 150 min after oleic acid injection, PaO2 changed from 193 +/- 7 (mean +/- SEM) to 55 +/- 4 torr, venous admixture from 3 +/- 1% to 52 +/- 5%, cardiac index from 4.1 +/- 0.3 to 3.1 +/- 0.3 L/min X m2, mean pulmonary artery pressure from 13 +/- 1 to 17 +/- 1 mm Hg, dynamic compliance from 90 +/- 8 to 46 +/- 7 ml/cm H2O, and EVLW from 165 +/- 25 to 750 +/- 92 ml/m2. Administration of perindopril diacid reduced systemic BP by 20% but did not affect other hemodynamic variables, blood gases, or dynamic compliance. Maximum increases in EVLW were from 169 +/- 16 to 615 +/- 54 ml/m2 in the pretreated group and from 188 +/- 23 to 675 +/- 56 ml/m2 in the treated group (no significant difference from the control group). However, pretreatment with perindopril diacid significantly (p less than .05) slowed the rise in EVLW, which was lower 60 and 90 min after oleic acid injection compared to untreated dogs. Plasma renin activity and angiotensin I concentration increased after oleic acid injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Chronic treatment with the angiotensin I converting enzyme inhibitor, perindopril, restores the lower limit of autoregulation of cerebral blood flow in the awake renovascular hypertensive rat.

Chronic hypertension shifts the lower limit of cerebral blood flow autoregulation to a higher pressure level. Although acute administration of angiotensin converting enzyme inhibitors restores the lower limit of cerebral blood flow autoregulation the chronic effects have not received much attention. We studied the effect of the angiotensin converting enzyme inhibitor, perindopril, on mean arterial pressure, basal cerebral blood flow and cerebral blood flow autoregulation in renovascular hypertensive (two-kidney, one clip model) and normotensive male Wistar rats. Seven weeks after renal artery clipping or sham operation rats received daily intraperitoneal injections of perindopril. The dose was increased from 1 to 8 mg/kg over the first 4 weeks until blood pressure was normalized. Chronic renovascular hypertension caused a marked shift in the lower limit of cerebral blood flow autoregulation but did not alter basal cerebral blood flow. Treatment of hypertensive rats with perindopril normalized blood pressure and restored cerebral blood flow autoregulation. Chronic treatment of normotensive rats with perindopril increased basal cerebral blood flow. In conclusion, chronic treatment of renovascular hypertensive rats with perindopril causes a shift in the lower limit of cerebral blood flow autoregulation towards the value observed in normotensive rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

The effect of perindopril on blood pressure in humans on different sodium intakes.

Perindopril is a new inhibitor of converting enzyme activity with a prolonged half-life. Thirty-two patients with essential hypertension and a diastolic blood pressure greater than 95 mm Hg were stratified into two groups according to their 24 h urine sodium excretion. They were randomized in a double-blind fashion to placebo or perindopril and a dose titration made in steps of 2, 4, 6, and 8 mg given once daily at weekly intervals. The goal diastolic blood pressure was 90 mm Hg. Goal blood pressure was achieved in 11 of 16 patients on perindopril and 3 of 6 patients on placebo. Perindopril caused a fall in BP of 22/11 (supine) and 27/14 (erect) mm Hg while the placebo group had falls of 3/2 (supine) and 3/0 (erect) mm Hg. Most of the blood pressure fall occurred in the first week of therapy with 2 mg/day. Side effects were few and occurred mainly in the placebo phase. There was no alteration in urine protein, white cell count, plasma urea, or creatinine. The fall in blood pressure achieved at the end of the titration or with 2 mg did not differ between the two groups. There was no correlation between blood pressure response and 24 h urine sodium or plasma renin activity. These results indicate that perindopril is an effective antihypertensive drug that appears to work equally well in patients on high or low sodium intake.

Aged↗
PubMed1994

Effects of early and late therapy with perindopril on survival and myocardial inotropic state in experimental dilated cardiomyopathy.

We wished to test (a) whether single-drug therapy with a low dose of the angiotensin-converting enzyme (ACE) inhibitor perindopril has the capacity to improve early survival of the cardiomyopathic Syrian hamster (CSH); (b) whether early treatment with perindopril modifies CSH survival to a greater extent than perindopril treatment initiated later in the course of the disease; and (c) the effects of early and late perindopril therapy on the intrinsic contractility of left ventricular (LV) papillary muscle. We studied CSH from the Bio 53.58 dilated strain (n = 76), in which myocardial necrosis is known to develop from age 30 days, whereas congestive heart failure (CHF) is observed only after age 6 months. Animals were randomly assigned to three groups. In early-treated animals, perindopril (1 mg/kg body weight once daily in distilled water) was administered by force-feeding from age 1 month to 9 months (PE1, n = 21). Animals receiving delayed treatment received distilled water from age 1 month to 6 months, followed by 1 mg/kg body weight from age 6 to 9 months (PE2, n = 34). Controls received distilled water from age 1 month to 9 months (C, n = 21). At endpoint (9 months), mechanical properties of LV papillary muscles and serum ACE activity were studied in a subgroup of 32 CSH (C, n = 8; PE1, n = 10; and PE2, n = 14). Maximum unloaded shortening velocity, maximum extent of systolic shortening in twitch with preload only, and normalized peak of isometric active force were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Inhibitory effect of perindopril, a novel angiotensin-converting enzyme inhibitor, on neointima formation after balloon injury in rats and cholesterol-fed rabbits.

We investigated the effect of perindopril, a novel angiotensin-converting enzyme (ACE) inhibitor, on neointima formation in vessel walls after balloon injury in rats (carotid artery) and cholesterol-fed rabbits (thoracic aorta). Continuous treatment with perindopril significantly reduced neointima formation in both species, as compared with the control group: intima/media (I/M) ratio (rats -62%; p < 0.001; rabbits -25%, p < 0.05); neointima area (rats -65%, p < 0.01; rabbits -24%, p < 0.05). These changes involved reduction of intimal smooth muscle cells (SMC) in rats and of macrophages in rabbits. Furthermore, perindopril also significantly decreased ACE activity in both aortic tissue and serum [11.38 +/- 0.87 vs. 34.93 +/- 6.44 pmol His-Leu (HL)/mg/min (p < 0.01) and 2.79 +/- 0.28 vs. 38.50 +/- 5.41 pmol HL/mg/min (p < 0.001), respectively], aortic contraction evoked by angiotensin I (AI) and mean blood pressure (BP, 84.9 +/- 3.5 vs. 109.3 +/- 3.8 mm Hg, p < 0.001) as compared with control values. These results indicate that perindopril may reduce neointima formation by suppressing the aortic renin-angiotensin system (RAS). These findings indicate that perindopril may be capable of preventing restenotic lesions after angioplasty in humans [corrected].

Angioplasty, Balloon↗
PubMed1991

Single dose pharmacokinetics of perindopril and its metabolites in hypertensive patients with various degrees of renal insufficiency.

1 Perindopril is a prodrug which is hydrolysed in vivo to the active metabolite perindoprilat, an angiotensin-converting enzyme inhibitor. Perindoprilat glucuronide is also found in plasma. 2 The pharmacokinetics of perindopril and its metabolites were studied after administration of a single 4 mg dose to hypertensive patients with various degrees of renal failure. 3 The absorption and elimination of perindopril were not influenced by the degree of renal failure. 4 The mean area under the serum concentration-time curve of the active metabolite perindoprilat increased from 93 ng ml-1 h in subjects with normal renal function to 1106 ng ml-1 in patients with severe renal failure, whereas its half-life varied from 5.0 to 27.4 h. 5 In the same subjects, the mean area under the curve of perindoprilat glucuronide increased from 78 to 513 ng ml-1 h, while its half-life varied from 1.8 h to 7.7 h. 6 Perindopril, perindoprilat, and perindoprilat glucuronide were dialysable. 7 The extent and duration of serum angiotensin-converting enzyme inhibition was augmented in renal failure. The mean area under the inhibition time curve (extrapolated to infinity) increased from 2490%.h in subjects with normal renal function to 42241 %.h in patients with severe renal impairment. The half-life of inhibition varied from 12.1 h to 100.4 h. This effect of renal failure on the pharmacodynamics of perindoprilat was more pronounced than its influence on perindoprilat kinetics. 8 In view of the important influence of renal impairment on the elimination and action of the active substance perindoprilat, a dosage reduction of perindopril is proposed in in patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The pharmacokinetics of perindopril and its effects on serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure.

1. Perindopril, an orally active angiotensin converting enzyme inhibitor, was given to 23 hypertensive patients with stable chronic renal failure for 15 days. The dose of perindopril was 2 or 4 mg once a day according to the degree of renal failure. The creatinine clearance of the patients ranged from 6 to 67 ml min-1 1.73 m-2. The pharmacokinetics of perindopril and perindoprilat, its active metabolite, were studied after acute and chronic administration of perindopril. 2. The drug was well tolerated and creatinine clearance was unaltered by treatment. 3. In both groups, steady-state was reached within 3 days of chronic treatment. 4. After both acute and chronic drug administration renal impairment had no effect on perindopril pharmacokinetics but the pharmacokinetics of perindoprilat were altered significantly. After chronic administration the serum accumulation ratio was 1.81 in patients with mild renal failure and 5.35 in patients with severe renal failure. Chronic administration did not modify the renal clearance of perindoprilat nor its elimination half-life. 5. A significant correlation between the renal clearance of perindoprilat and creatinine clearance was observed (r = 0.87 first dose, r = 0.83 last chronic dose). 6. A non-linear relationship between serum perindoprilat concentration and inhibition of angiotensin converting enzyme was described by a modified Hill equation. Values of IC50 were 1.11 +/- 0.07 micrograms I-1 (mean +/- s.d.) in patients with severe renal failure and 1.81 +/- 0.20 micrograms l-1 in patients with moderate renal failure. Chronic administration increased maximal inhibition and decreased the time to maximal inhibition only in patients with severe renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2005

Perindopril: the reasonable choice in patients with coronary artery disease.

Recent studies in patients with coronary artery disease (CAD) have suggested that angiotensin-converting enzyme (ACE) inhibitors may have benefits beyond blood pressure reduction alone. Increased arterial stiffness, itself an emerging risk factor for CAD, adversely influences ventricular vascular interaction, leading to an increased central aortic pulse pressure. A number of recent studies have demonstrated a clear relationship between central pulse pressure and angiographic CAD. Furthermore, aortic stiffness also correlates with CAD. These studies are consistent with the hypothesis that central aortic stiffness may promote the development of CAD and that therapeutic intervention targeted at reducing arterial stiffness may be of benefit in patients with CAD. The ACE inhibitor, perindopril, has been shown to decrease arterial stiffness, largely independently of any effect on peripheral blood pressure. Results of the recent REASON study demonstrate that perindopril, in combination with indapamide, reduces central systolic and pulse pressure to a greater degree than the beta-blocker atenolol and that this effect is due to improved arterial stiffness and decreased wave reflection. In addition to its other beneficial effects, such as improved endothelial function and decreased inflammation, these haemodynamic effects of perindopril may therefore have contributed to the decrease in cardiovascular events seen in patients in the EUROPA study. Overall, perindopril, in addition to lowering peripheral blood pressure, decreases arterial stiffness and central pulse pressure. In individuals with CAD, perindopril would thus appear to be a very reasonable choice.

Adrenergic beta-Antagonists↗
PubMed1992

Clinical efficacy of perindopril in hypertension.

1. Perindopril's effectiveness in mild to moderate hypertension was evaluated in three studies. 2. Perindopril was more effective than sodium restriction in reducing blood pressure, and the effects were additive. 3. Perindopril was as effective as atenolol in reducing blood pressure, and was well tolerated. 4. Perindopril lowered blood pressure to the same extent as enalapril at peak drug levels but had a greater effect at the trough level of the drugs. 5. Perindopril is an effective antihypertensive agent with an acceptable side-effect profile in people with hypertension.

Aged↗
PubMed2000

The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson's disease.

BACKGROUND: Animal studies have demonstrated an interaction within the striatum between the angiotensin and dopaminergic systems. In rats, the angiotensin converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier and increases striatal dopamine synthesis and release. In humans, angiotensin type 1 receptors have been found on dopaminergic neurons in the substantia nigra and striatum. In Parkinson's disease, there is a marked reduction of these receptors associated with the nigrostriatal dopaminergic neuron loss. AIMS: We performed a double blind placebo controlled crossover pilot study in seven patients to investigate the effect of the ACE inhibitor, perindopril on the clinical features of moderately severe Parkinson's disease. RESULTS: After a four week treatment period with perindopril, patients had a faster onset in their motor response to L-dopa and a reduction in 'on phase' peak dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more 'on' periods during their waking day in their movement diary, p=0.007. Perindopril was well tolerated without any significant postural hypotension or renal dysfunction. CONCLUSIONS: These results suggest that ACE inhibitors such as perindopril may have a place in the management of motor fluctuations and dyskinesia in Parkinson's disease and justify further study.

Adult↗
PubMed1990

Pharmacokinetics of perindopril and its metabolites in healthy volunteers.

Perindopril, an angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to its active diacid metabolite, perindoprilat and to a perindoprilat glucuronide. The pharmacokinetic parameters of perindopril, perindoprilat and perindoprilat glucuronide were evaluated after single administration to healthy volunteers (N = 12) of 8 mg of perindopril tert-butylamine salt by oral route (treatment A), by intravenous route (bolus in 5 min, treatment B) and of an equimolar dose of perindoprilat (6.1 mg) by intravenous route (infusion over 2 h, treatment C). The treatments were administered as a randomised 3-way cross-over design. Plasma samples were collected up to 96 h and urines up to 120 h. Perindopril is rapidly absorbed with an oral bioavailability of 95% and is mainly eliminated by metabolic processes. The formation of perindoprilat is slow and about 20% of the available parent drug is transformed into this metabolite. Elimination profile of perindoprilat is biphasic, with a rapid renal excretion of the free fraction and a long terminal half-life of the fraction bound to ACE. Perindoprilat glucuronide is mainly obtained from perindopril by a pre-systemic first pass metabolism.

Administration, Oral↗
PubMed1991

Comparison between perindopril and nifedipine in hypertensive and normotensive diabetic patients with microalbuminuria. Melbourne Diabetic Nephropathy Study Group.

OBJECTIVE: To compare the efficacy of angiotensin converting enzyme inhibition with calcium antagonism in diabetic patients with microalbuminuria. DESIGN: Randomised study of diabetic patients with microalbuminuria treated with perindopril or nifedipine for 12 months and monitored for one or three months after stopping treatment depending on whether they were hypertensive or normotensive. Patients were randomised separately according to whether they were hypertensive or normotensive. SETTING: Diabetic clinics in three university teaching hospitals. PATIENTS: 50 diabetic patients with persistent microalbuminuria. In all, 43 completed the study: 30 were normotensive and 13 hypertensive; 19 had type I diabetes and 24 had type II diabetes. INTERVENTIONS: For 12 months 20 patients were given perindopril 2-8 mg daily and 23 were given nifedipine 20-80 mg daily. MAIN OUTCOME MEASURES: Albumin excretion rate, blood pressure, and glomerular filtration rate. RESULTS: Both perindopril and nifedipine significantly reduced mean blood pressure. During treatment there was no significant difference between those treated with perindopril and those treated with nifedipine with respect to albuminuria or mean blood pressure. Stopping treatment with both drugs was associated with a sustained increase in albuminuria and mean blood pressure. There was a significant correlation between mean blood pressure and albuminuria and also between the reduction in mean blood pressure and the decrease in albuminuria during treatment with both drugs. In hypertensive patients both drugs caused significant decreases in mean blood pressure and albuminuria. In normotensive patients there was no significant reduction in albuminuria with either regimen. CONCLUSIONS: In diabetic patients with microalbuminuria blood pressure seems to be an important determinant of urinary albumin excretion. Perindopril and nifedipine have similar effects on urinary albumin excretion, both preventing increases in albuminuria in normotensive patients and decreasing albuminuria in hypertensive patients.

Adolescent↗
PubMed2006

Cost effectiveness of perindopril in reducing cardiovascular events in patients with stable coronary artery disease using data from the EUROPA study.

BACKGROUND: The EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease (EUROPA) trial has recently reported. OBJECTIVE: To assess the cost effectiveness of perindopril in stable coronary heart disease in the UK. METHODS: Clinical and resource use data were taken from the EUROPA trial. Costs included drugs and hospitalisations. Health-related quality of life values were taken from published sources. A cost-effectiveness analysis is presented as a function of the risk of a primary event (non-fatal myocardial infarction, cardiac arrest or cardiovascular death) in order to identify people for whom treatment offers greatest value for money. RESULTS: The median incremental cost of perindopril for each quality-adjusted life year (QALY) gained across the heterogeneous population of EUROPA was estimated as 9700 pounds(interquartile range 6400-14,200 pounds). Overall, 88% of the EUROPA population had an estimated cost per QALY below 20,000 pounds and 97% below 30,000 pounds. For a threshold value of cost effectiveness of 30,000 pounds per QALY gained, treatment of people representing the 25th, 50th (median) and 75th centiles of the cost effectiveness distribution for perindopril has a probability of 0.999, 0.99 and 0.93 of being cost effective, respectively. Cost effectiveness was strongly related to higher risk of a primary event under standard care. CONCLUSIONS: Whether the use of perindopril can be considered cost effective depends on the threshold value of cost effectiveness of healthcare systems. For the large majority of patients included in EUROPA, the incremental cost per QALY gained was lower than the apparent threshold used by the National Institute for Health and Clinical Excellence in the UK.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Perindopril effect on uncoupling protein and energy metabolism in failing rat hearts.

Uncoupling proteins, inner mitochondrial membrane proton transporters, are important for regulating myocardial energy efficiency. We investigated the effects of the ACE inhibitor perindopril on cardiac performance, myocardial energy efficiency, and uncoupling protein expression in an aortic regurgitation rat model. Twenty male Sprague-Dawley rats, in which aortic regurgitation was produced, were divided into untreated and perindopril-treated (5 mg x kg(-1) x d(-1)) rats. The treatments were initiated 3 days after operation. Ten control rats were sham-operated. Measurements of blood pressure and echocardiography were repeated before and 100 days after operation (endpoint). Left ventricular uncoupling protein-2 expression, creatine phosphate, and adenosine triphosphate were measured at endpoint. In perindopril-treated rats, systolic and diastolic blood pressure decreased after treatment (92+/-4/65+/-2 mm Hg). At endpoint, left ventricular end-diastolic dimension in untreated (10.7+/-0.2 mm) and treated rats (9.2+/-0.2 mm) was increased, and fractional shortening was reduced in untreated rats (28+/-1%) but did not change in treated rats (36+/-2%). Uncoupling protein-2 mRNA expression increased in untreated rats (3.7-fold) and was suppressed by perindopril (1.5-fold). The creatine phosphate was reduced in untreated rats (10.6+/-0.7 micro mol/g) but not in treated rats (15.9+/-2.0 micro mol/g). In the chronic stage of aortic regurgitation, perindopril improved cardiac performance and myocardial energy efficiency, in which the suppression of uncoupling protein-2 may play an important role.

Adenosine Triphosphate↗
PubMed1995

Comparison of perindopril and amlodipine in cyclosporine-treated renal allograft recipients.

The objective of this study was to compare the antihypertensive efficacy and influence on renal function of perindopril and amlodipine in cyclosporine-treated renal allograft recipients with mild to moderate hypertension. We conducted a randomized, double-blind, double-dummy crossover trial in ambulatory patients. Four phases were conducted: 2 weeks on placebo, 8 weeks of maintenance (perindopril or amlodipine), and 2 weeks of washout between treatment periods. Ten hypertensive patients with stable renal allograft function transplanted more than 6 months previously and receiving cyclosporine as part of their immunosuppressive regimen were studied. The patients were allocated to perindopril (2 or 4 mg/d) and amlodipine (5 mg/d) in a random sequence. If office diastolic pressure was greater than or equal to 90 mm Hg after 4 weeks, the dosage was doubled and continued for another 4 weeks. The main outcome measures were office and 24-hour ambulatory blood pressure changes after 8 weeks of active treatment and treatment and time effect on glomerular filtration rate and effective renal plasma flow. Perindopril and amlodipine were equally effective in lowering office blood pressure and similarly efficacious for the 24-hour period of the day. Neither drug affected glomerular filtration rate or effective renal plasma flow. Both agents demonstrated equivalent capacity (time x treatment, P = .955) to reverse renal vascular resistance (amlodipine from 0.35 +/- 0.02 to 0.30 +/- 0.02 mm Hg/mL per minute per 1.73 m2; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01) (time effect of all treatments together, P = .043).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1998

Perindopril treatment affects both preglomerular renal vascular lumen dimensions and in vivo responsiveness to vasoconstrictors in spontaneously hypertensive rats.

We have previously shown that chronic treatment with angiotensin-converting enzyme inhibition (ACEI) did not reverse hypertrophy of the renal arterial wall in spontaneously hypertensive rats (SHR). In this study we determined the effects of perindopril on the functional properties of the renal vasculature in vivo and on its resistance to flow at maximal dilatation in vitro, a measure of vessel lumen diameter. Two groups of SHR were studied: untreated or treated with perindopril (3 mg/kg per day) in their drinking water from 4 weeks of age. At 10 weeks, (1) vessel lumen characteristics were assessed using a maximally dilated in vitro isolated kidney perfusion and (2) the renal vasoconstrictor responses to bolus doses of vasoactive agents (angiotensin II and phenylephrine) administered into the renal artery were measured in vivo (anesthetized rats). Mean arterial pressure was significantly lower in conscious SHR treated with perindopril (132+/-2 versus 97+/-2 mm Hg, P<.001). In vitro, the pressure-flow relationship and the pressure-glomerular filtration rate relationship were both shifted significantly to the left (P<.001). The perindopril-treated kidneys began filtering at a significantly lower threshold perfusion pressure than nontreated controls (P<.001). In vivo, renal vasoconstrictor responses to increasing doses of both vasoconstrictor agents were significantly less marked in the perindopril-treated SHR than in untreated SHR (P<.05). Thus, chronic ACEI increased average renal vessel lumen diameter in SHR, predominantly in preglomerular vessels, and reduced renal vasoconstrictor responsiveness in vivo, findings compatible with remodeling of the preglomerular vasculature around a greater lumen.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Perindopril reduces blood pressure but not cerebral blood flow in patients with recent cerebral ischemic stroke.

BACKGROUND AND PURPOSE: The relationship between high blood pressure and the incidence of stroke is well established. Currently the effects of lowering blood pressure in patients with established cerebrovascular disease is undetermined, and there is continuing concern regarding the treatment of patients soon after a stroke event. Angiotensin-converting enzyme inhibitors maintain cerebral blood flow despite lowering blood pressure in patients with heart failure and otherwise uncomplicated hypertension. We tested the hypothesis that perindopril, an angiotensin-converting enzyme inhibitor with a gradual onset of action and a minimal first-dose hypotensive effect, lowers blood pressure without adversely affecting cerebral blood flow in patients 2 to 7 days after symptoms of cerebral infarction. METHODS: Patients were randomized to receive 15 days of oral perindopril (4 mg) or placebo in a double-blind study. Blood pressure was monitored semiautomatically. Cerebral blood flow was calculated from internal carotid artery and vertebral Doppler ultrasound, supplemented by middle cerebral artery blood velocities. RESULTS: Twenty-four patients completed the protocol; four additional patients were withdrawn for reasons unrelated to treatment. Patients on perindopril had a placebo-corrected reduction in blood pressure of 19/11 mm Hg. Blood pressure remained reduced after 2 weeks of treatment. In contrast, total cerebral blood flow was unaffected by perindopril. Neurological symptoms improved similarly in both groups. CONCLUSIONS: Perindopril was well tolerated and effectively reduced blood pressure without reducing carotid territory blood flow in patients with symptoms of recent cerebral ischemia.

Aged↗
PubMed2002

Perindopril alters vascular angiotensin-converting enzyme, AT(1) receptor, and nitric oxide synthase expression in patients with coronary heart disease.

Angiotensin-converting enzyme inhibitors (ACEi) reduce cardiovascular morbidity and mortality by improving coronary perfusion, reducing ventricular hypertrophy and remodeling, and preventing progression of coronary atherosclerosis. However, the cellular mechanisms underlying the beneficial effects of ACEi are not fully understood. We studied the in vivo effects of ACE inhibition with perindopril on cellular expression of ACE, AT(1) receptors and 2 nitric oxide synthase (NOS) isoforms, endothelial (eNOS) and inducible NOS (iNOS), in human blood vessels using quantitative in vitro autoradiography and immunocytochemistry. Seven patients with ischemic heart disease were treated with perindopril (4 mg/d) for up to 5 weeks before elective coronary bypass surgery, whereas controls did not receive the ACEi (n=7). Perindopril decreased plasma ACE by 70% and the plasma angiotensin II to angiotensin I ratio by 57% and reduced vascular ACE to approximately 65% of control levels in both endothelium and adventitia. By contrast, AT(1) receptor binding in vascular smooth muscle cells was increased by 80% in patients treated with perindopril as confirmed by immunocytochemistry. eNOS was expressed primarily in endothelial cells, whereas little iNOS expression occurred in vascular smooth muscle cells of untreated patients. Both eNOS and iNOS expression seemed to increase during perindopril treatment. These results suggest that suppression of angiotensin II formation in the vascular wall and increased expression of eNOS and iNOS during ACE inhibition may be beneficial in reversing endothelial dysfunction in patients with cardiovascular disease. Because vascular AT(1) receptor expression is increased during chronic ACE inhibition, more clinical studies are required to determine whether it is necessary to combine ACE inhibitors and AT(1) receptor antagonists in clinical management of heart failure, coronary heart disease, and hypertension

Adult↗