Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Perindopril”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1990

A double blind comparison of perindopril and atenolol in essential hypertension.

A multicentre randomised double-blind trial was performed in order to compare the therapeutic efficacy and acceptability of the angiotensin converting enzyme (ACE) inhibitor perindopril with those of atenolol in mild to moderate hypertension. After one month of placebo, 173 patients with supine diastolic blood pressure (DBP) between 95 and 125 mmHg were randomised to receive perindopril 4 mg once daily or atenolol 50 mg once daily. Monthly assessments were made for three months. Treatment was adjusted at these visits if supine DBP was greater than 90 mmHg; the dose was first doubled (8 mg perindopril or 100 mg atenolol once daily) and then hydrochlorothiazide was added. The pretreatment blood pressure levels were similar in both groups. Supine DBP was 105.5 +/- 0.9 mmHg (n = 85) in the perindopril group and 106.9 +/- 0.9 mmHg (n = 88) in the atenolol group. At the end of the third month, the study target blood pressure (supine DBP less than or equal to 90 mmHg) was achieved in a significantly (P = 0.006) larger percentage of patients in the perindopril group (78%) than in the atenolol group (58%). This appeared to be due to a greater potentiation of the antihypertensive effect by the addition of diuretic to perindopril than to atenolol. The fall in systolic blood pressure was significantly greater in the perindopril group than in the atenolol group (supine: 26.5 +/- 2.0 mmHg vs. 20.6 +/- 2.0 mmHg; P = 0.042) although the fall in DBP was comparable (supine: perindopril 17.4 +/- 0.9 mmHg, atenolol 15.6 +/- 1.1 mmHg; P = 0.195).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Haemodynamic effects of perindopril in essential hypertension.

Blood pressure, forearm arterial haemodynamics and echocardiographic parameters were studied in patients with sustained essential hypertension before and after administration of the ACE inhibitor, perindopril. In a single blind study versus placebo, perindopril significantly reduced BP and at the same time increased brachial artery diameter, blood flow and compliance. As part of the haemodynamic investigation, a 5 minute wrist occlusion was performed. During this period, blood flow velocity and arterial diameter decreased but the reduction in diameter was smaller with perindopril after one year's treatment showing an increase in brachial artery diameter. This result indicates that the increase in brachial arterial diameter following perindopril could not be explained solely on the basis of a flow dependent dilation. When perindopril was withdrawn after three months of treatment and replaced by placebo for four weeks, BP and forearm arterial haemodynamics returned towards baseline values. However, cardiac mass which was significantly decreased after perindopril remained decreased four weeks after cessation of treatment. In the seven normalised patients, perindopril was continued for one year; arterial compliance remained increased and cardia mass diminished. The study showed that the arterial changes caused by perindopril involved a drug-related relaxation of arterial smooth muscle and that there was a differential response in cardiac and arterial changes following long term treatment.

Adult↗
PubMed1988

Treatment for one year with perindopril: effect on cardiac mass and arterial compliance in essential hypertension.

Blood pressure, forearm arterial haemodynamics and echocardiographic parameters were studied in patients with sustained essential hypertension before and after administration of the angiotensin converting enzyme (ACE) inhibitor perindopril for 1 year. Perindopril significantly reduced blood pressure and at the same time increased brachial artery blood flow, diameter and compliance. As part of the haemodynamic investigation, a 5-min period of wrist occlusion was performed. Blood flow velocity decreased significantly to the same extent with perindopril and with placebo, but the corresponding reductions in arterial diameter were smaller with perindopril than with placebo, indicating that the increase in diameter following perindopril could not be explained solely on the basis of a flow-dependent dilation. After 3 months, treatment was stopped for 4 weeks. Blood pressure and forearm arterial haemodynamics returned towards baseline values. However, cardiac mass, which was significantly decreased after perindopril administration, remained decreased 4 weeks after cessation of treatment. In seven responder patients, perindopril was continued as sole therapy for 8 months. Arterial compliance remained elevated and cardiac mass diminished. The study showed that the arterial changes caused by perindopril involved a drug-related relaxation of arterial smooth muscle and that there was a differential response in cardiac and arterial changes following long-term treatment.

Adult↗
PubMed1996

Perindopril treatment prevents the loss of endothelial nitric oxide function and development of neo-intima in rabbits.

An atheroma-like neo-intima was produced by positioning a flexible collar around the common carotid arteries of normocholesterolaemic rabbits. Vessel segments taken from the mid-region of the collared and control region of the same artery were studied 7 days after surgery. Placebo rabbits were provided ab libitum with regular tap water, and treated animals were supplied with water containing perindopril (0.3 mg/kg/day) for 14 days. Perindopril treatment reduced plasma angiotensin converting enzyme (ACE) activity by 88%, but did not significantly alter arterial blood pressure or heart rate. In control rings from placebo rabbits perindoprilat in vitro (0.1-1.0 microM) reduced the sensitivity to angiotension I up to 20-fold but did not affect that of angiotensin II. In placebo rabbits, the collared arterial segments were approximately five-fold more sensitive to the vasoconstrictor action of 5-HT (P < 0.05) than the corresponding control segments. Perindopril treatment did not prevent the supersensitivity of the collared vessels to 5-HT. Development of the lesion in placebo or perindopril-treated rabbits did not alter the vascular sensitivity to either angiotensin I (10(-9)-10(-5)M) or angiotensin II (10(-10)-10(-6)M). The vasorelaxant action of sodium nitroprusside was similar in collared and control rings, whereas the maximum endothelium-dependent vasorelaxant response to acetylcholine was reduced from 68 +/- 5% in control rings, to 44 +/- 8% (mean +/- S.E.M., n = 9, P < 0.05) in collared rings of placebo-treated rabbits. In the perindopril-treated animals, this impairment of relaxation was restored in collared vessels and was no longer significantly different from the control sections. In contrast, perindoprilat in vitro (1.0 microM) did not alter the vasorelaxant response to acetylcholine in control or collared rings in a separate series of placebo rabbits. Morphologically, vessel segments taken from the centre of the collared artery of all placebo rabbits showed a thickened intima filled with cells that had the appearance of synthetic-state smooth muscle. The intimal/medial cross-sectional area ratio was reduced from 0.11 +/- 0.02 (n = 10) in placebo rabbits to 0.05 +/- 0.01 (n = 9) in perindopril-treated rabbits, whereas cross-sectional area of media of the collared vessels was similar in the two groups. Thus ACE may have important roles in the initiation and progression of atheroma-like lesions. Inhibition of ACE with perindopril reduces intimal thickening and restores the defective vasodilatation induced by the endothelial-dependent vasodilator, acetylcholine.

Angiotensin II↗
PubMed1995

Clinical acceptability of ACE inhibitor therapy in mild to moderate hypertension, a comparison between perindopril and enalapril.

The aim of this 3-month double-blind study was to assess the antihypertensive effect and acceptability of perindopril in comparison with enalapril in patients with mild to moderate essential hypertension. After a 4-week placebo run-in period, 161 patients with supine diastolic blood pressure (DBP) between 95 and 115 mmHg were randomized to receive perindopril 4 mg or enalapril 10 mg once daily. If supine DBP was higher than 90 mmHg, treatment was adjusted monthly, first by doubling the dose and then by addition of hydrochlorothiazide 12.5 mg. After 3 months of active treatment the decrease in supine and standing blood pressures was statistically significant within both groups but was not statistically different between groups. The percentage of patients (65%) who achieved supine DBP of < or = 90 mmHg in the perindopril group was not significantly different from the enalapril group (73%). Monotherapy resulted in control of supine DBP in 56% of the perindopril group and 58% of the enalapril group; the addition of hydrochlorothiazide resulted in control of supine DBP in 6% and 15% respectively. The number of withdrawals for adverse events was statistically significant between groups (0 in the perindopril group and 7 in the enalapril group, p = 0.01). During active treatment the most frequently reported complaints were headaches and cough; there was not statistically difference between groups. Changes in laboratory parameters were minor and not significantly different between the two groups except for serum glucose, potassium, and triglyceride levels. In conclusion, there was no significance between perindopril and enalapril in terms of efficacy. Clinical acceptability seems to be better in the perindopril group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2004

Effects of the angiotensin-I converting enzyme inhibitor perindopril on tumor growth and angiogenesis in head and neck squamous cell carcinoma cells.

PURPOSE: Recently, it has been reported that angiotensin-I converting enzyme (ACE) inhibitors have anticancer activity. In particular, the ACE inhibitor, perindopril, significantly inhibits tumor growth and angiogenesis in hepatocellular carcinoma cells along with suppression of the VEGF level. However, the mechanisms of suppression of the VEGF level are still unclear, and there are no previous reports on this subject related to head and neck squamous cell carcinoma (HNSCC). In some previous studies, angiotensin II, which is produced from angiotensin I by ACE, directly stimulates VEGF expression. METHODS: In the present study, we focused upon angiotensin II, and investigated the effect of perindopril on VEGF expression, angiogenesis, and tumor development of HNSCC with in vitro and in vivo studies. RESULTS: In the in vitro cell proliferation assays, there was no significant difference between the perindopril-treated group and the control group. However, the perindoprilat-treated group showed a significant reduction in mRNA expression of VEGF and inhibited the induction activity of the VEGF promoter in comparison to the control group. Perindoprilat treatment also significantly suppressed angiotensin II production in vitro. In the in vivo studies, perindopril had a significant inhibitory effect on tumor growth, and reduced blood vessel formation surrounding the tumors. CONCLUSIONS: Our findings suggest that perindopril has no direct cytotoxicity against tumor cells, but has a potential to inhibit tumor growth due to suppression of VEGF-induced angiogenesis in vivo. Angiotensin II might have an important role in carcinogenesis, and the antiangiogenic activity of perindopril is at least partly mediated by angiotensin II inhibition. The ACE inhibitor perindopril has clinical potential as a useful antitumor agent.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Effect of angiotensin-converting enzyme inhibitor perindopril on interneurons in MPTP-treated mice.

We examined the effects of perindopril on the dopaminergic system in mice after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. The mice received four intraperitoneal injections of MPTP at 1-h intervals. Administration of perindopril showed dose-dependent neuroprotective effects against striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletion 3 days after MPTP treatment. Our immunohistochemical study showed that MPTP can severe damage in tyrosine hydroxylase (TH)-immunoreactive neurons after MPTP treatment. The administration of perindopril significantly attenuated MPTP-induced substantia nigra and striatal damage. The present study also showed that the immunoreactivity of parvalbumin (PV)- or neuronal nitric oxide synthase (nNOS)-positive cells in the substantia nigra was decreased 7 days after MPTP treatment, whereas no significant changes were observed in these cells of the striatum throughout the experiments. The administration of perindopril significantly attenuated MPTP-induced decrease of the PV- or nNOS-immunoreactivity in the nigral cells. In double-labeled immunostaining with anti-PV and anti-nNOS antibody, PV-immunoreactive cell bodies and fibers were not double-labeled for nNOS-immunoreactive cell bodies and fibers in both the striatum and substantia nigra after MPTP treatment. Furthermore, PV- or nNOS-immunoreactive cell bodies and fibers in both the striatum and substantia nigra were not double-labeled for TH-immunoreactive cell bodies and fibers. These results demonstrate that the ACE inhibitor perindopril has a dose-dependent protective effect against MPTP-induced striatal dopamine, DOPAC and HVA depletion in mice. The present study also demonstrates that perindopril is effective against MPTP-induced degeneration of the nigral neurons and interneurons. Furthermore, our immunohistochemical study suggests that PV-immunoreactive cells and nNOS-immunoreactive cells are different interneurons in both the striatum and substantia nigra. Thus, our results provide further evidence that the ACE inhibitor perindopril may offer a novel therapeutic strategy for Parkinson's disease (PD).

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1996

Metabolic neutrality of perindopril: focus on insulin sensitivity in overweight patients with essential hypertension.

To assess the effects of antihypertensive treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril on insulin sensitivity, plasma insulin, and lipoprotein metabolism in overweight hypertensive patients, we measured the insulin sensitivity index (SI, determined according to the minimal model method of Bergman), fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure (BP) in 30 overweight [mean body mass index (BMI) 30.9 kg/m2], nondiabetic patients with essential hypertension after a 4-week run-in period and after 6 weeks of perindopril (n = 20) or placebo (n = 10) administered in a double-blind fashion. Furthermore, we estimated their state of physical fitness using the Conconi bicycle ergometer test before and after perindopril or placebo administration. SI was low in our study population (3.2 vs. 13.3 10(-4) ml.microU-1.min-1 in normal lean control subjects). It did not differ between the perindopril and placebo group after the placebo run-in period (3.1 vs. 3.3 x 10(-4) ml.microU-1.min-1) and was not influenced by perindopril (3.3 x 10(-4) ml.microU-1.min-1) or placebo (3.6 x 10(-4) ml.microU-1.min-1) treatment. Moreover, no significant changes were apparent in fasting plasma insulin and glucose, the areas under the glucose and insulin curves, the glucose disappearance rates, serum total triglycerides (TG), or cholesterol or lipoprotein cholesterol fractions between run-in and active treatment phases in the perindopril or the placebo group, respectively. Heart rate (HR), body weight, and anaerobic threshold remained stable in both groups. Compliance, assessed by pill counting was > 90% in both groups at all visits. Therefore, the ACE inhibitor perindopril is neutral with regard to insulin sensitivity, plasma insulin and glucose, and lipoprotein metabolism in overweight, nondiabetic patients with essential hypertension.

Adult↗
PubMed1992

Effect of perindopril on the development of atherosclerosis in the cholesterol-fed rabbit.

1. The aim of the study was to examine the effect of the angiotensin-converting enzyme inhibitor perindopril on the development of atheroma in the cholesterol-fed rabbit. 2. The normal human carotid artery, like most large human arteries, has a preformed diffuse intimal thickening. To model this thickening, the right carotid artery of the 12-week-old rabbit had an expanded balloon catheter passed down it to remove the endothelium and partially damage the media. 3. Fourteen weeks after this operation, a myointimal thickening similar in almost all respects to the human intimal thickening had developed. The rabbits were then divided into six groups of six rabbits fed on: (i) a 1% cholesterol diet; (ii) a 1% cholesterol diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); (iii) a 1% cholesterol diet plus a non-hypotensive dose of perindopril (0.01 mg/kg per day); (iv) a normal diet; (v) a normal diet plus a hypotensive dose of perindopril (0.3 mg/kg per day); and (vi) a normal diet plus a non-hypotensive dose of perindopril (0.01 mg/kg per day). 4. After 6 weeks of treatment the animals were sacrificed. There were ameliorating effects of both hypotensive and non-hypotensive doses of perindopril on the development of plaques, as determined by the area of intima covered by Oil Red-O-staining plaque and light microscopy. 5. Cell culture studies indicated that perindopril has no effect on smooth muscle proliferation, but increases collagen and non-collagen synthesis by smooth muscle cells and decreases their binding of the atherogenic lipoprotein beta-very low density lipoprotein (beta-VLDL).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Differential efficacy of perindopril and enalapril in experimental diabetic nephropathy.

1. Treatment with angiotensin converting enzyme (ACE) inhibitors ameliorates human and experimental diabetic nephropathy, possibly as a result of changes in angiotensin II (AngII) and/or bradykinin concentrations. However, ACE is an indiscriminate enzyme, which hydrolyses numerous vasoactive peptides at two catalytic sites that are thought to be substrate specific. AngI is cleaved at the C-terminal site, bradykinin at both the C- and N-terminal sites, while other substrates may be preferentially cleaved at the N-terminal site. Of the various ACE inhibitors, some (e.g. perindopril) bind preferentially to the C-terminal site while others (e.g. enalapril) bind to both. We compared the efficacy of perindopril and enalapril in the diabetic SHR to determine whether all the benefits of ACE inhibition derive from changes in the concentrations of C-terminal related substrates. 2. Diabetes was induced by tail vein injection of streptozotocin (60 mg/kg) in 14 week old SHR. Blood glucose was maintained at 4-8 mmol/L by daily ultralente insulin injection and rats were randomized to control, enalapril (10 mg/kg per day) or perindopril (4 mg/kg per day) groups. Blood pressure, creatinine clearance and urinary protein excretion were monitored for 3 months. 3. Blood pressure in both treatment groups was lower than in control (perindopril P < 0.0001; enalapril P < 0.0001). Levels were marginally higher in the perindopril group than the enalapril group, although this difference was significant only in the second month (P < 0.025). Creatinine clearance was significantly lower in the perindopril group (0.44 +/- 0.05 mL/min) than in either the control rats (0.85 +/- 0.11 mL/min; P < 0.001) or the enalapril-treated group (0.66 +/- 0.05 mL/min; P < 0.005). Proteinuria was also lower in this group (4.3 +/- 0.9 mg/24h) than in the enalapril-treated (11.3 +/- 5.8 mg/24h; P < 0.05) or control groups (32.1 +/- 4.5 mg/24h; P < 0.0005). 4. The difference in efficacy between perindopril and enalapril that we have observed suggests that the benefits of ACE inhibition derive from changes in the concentrations of peptides catalysed by the C-terminal rather than the N-terminal site.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1997

Effect of angiotensin converting enzyme inhibition by perindopril on proteinuria of primary renal diseases.

Many primary renal diseases are associated with marked proteinuria resistant to immunosuppressive therapy. Short-term treatment with angiotensin converting enzyme (ACE) inhibitors may decrease proteinuria in these patients, but the long-term effect of these agents on urinary protein excretion is not known. We conducted a double-blind, parallel-design, placebo-controlled study of 1 year duration to evaluate the efficacy of the new ACE inhibitor, perindopril, in reducing proteinuria in patients with nephrotic syndrome due to histologically proven membranous and membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Half of the patients treated with perindopril displayed a decrease in urinary protein excretion from 6.1 +/- 1.0 to 1.2 +/- 0.5 g/24 h, and a rise in serum albumin levels. In the placebo group, protein excretion increased modestly and serum albumin level did not change. There was no difference between the responders and nonresponders to perindopril in age, blood pressure, level of creatinine clearance or urinary sodium excretion. However, the degree of proteinuria before treatment with perindopril was significantly (p < 0.01) higher in the nonresponders. In 3 patients in whom the treatment with perindopril was extended for 18-24 months, urinary protein excretion remained below 1 g/24 h. The data show that perindopril: (1) is an effective agent in the treatment of proteinuria of primary renal diseases; (2) the effect is sustained for up to 2 years if the administration of the drugs is maintained, and (3) this action of perindopril does not depend on the level of sodium intake.

Adult↗
PubMed1996

Cardiac transplantation, perindopril, and left ventricular hypertrophy in spontaneously hypertensive rats.

Angiotensin-converting enzyme inhibitors reduce blood pressure and cardiac mass but may also have a direct effect on myocardial growth. To test this hypothesis, we studied the effects of perindopril on the weight of transplanted hearts in which the left ventricle does not pump blood. Hearts were transplanted between littermate 10-week-old male spontaneously hypertensive rats, and recipients were treated for 2 weeks with vehicle (n = 10), perindopril (3 mg/kg per day) (n = 9), perindopril (3 mg/kg per day) plus the selective bradykinin B2 receptor antagonist Hoe 140 (500 micrograms/kg per day) (n = 13), or angiotensin II (200 ng/kg per minute) (n = 12). Perindopril reduced blood pressure and native left ventricular weight and also caused a significant decrease in the weight of the transplanted left ventricle compared with controls. Hoe 140 did not significantly alter blood pressure or native left ventricular weight of perindopril-treated rats but caused a significant increase in the weight of the transplanted left ventricle compared with rats treated with perindopril alone. Angiotensin treatment resulted in a significant increase in blood pressure and native left ventricular weight but no significant change in the weight of the transplanted left ventricle. Blood pressure and left ventricular weight for native but not for transplanted hearts were positively correlated. Therefore, in the absence of mechanical load, the weight of the left ventricle of spontaneously hypertensive rats responds little to angiotensin II but can be reduced by angiotensin-converting enzyme inhibition. The effect of perindopril on transplanted hearts of spontaneously hypertensive rats appears to depend on bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Neuroprotective effect of the angiotensin-converting enzyme inhibitor perindopril in MPTP-treated mice.

The angiotensin -converting enzyme (ACE) inhibitor perindopril has been shown to exert beneficial effects on the dopaminergic system. Here, we investigated the effects of perindopril on the dopaminergic system in mice after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment, in comparison with a Ca(2+) antagonist, amlodipine. Administration of perindopril showed dose-dependent neuroprotective effects against MPTP-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) depletion. However, administration of amlodipine showed no significant effects on striatal dopamine depletion after MPTP treatment. In our immunohistochemical studies with antibodies against tyrosine hydroxylase (TH), microtubule-associated protein 2a, b (MAP2), dopamine transporter (DAT), parvalbumin (PV), glial fibrillary acidic protein (GFAP) and Cu/Zn-superoxide dismutase (Cu/Zn-SOD), the administration of perindopril significantly attenuated MPTP-induced substantia nigra and striatal damage. This drug also blocked the increases in GFAP-positive astrocytes in the striatum and substantia nigra after MPTP treatment. Furthermore, the administration of perindopril showed a protective effect against the intense Cu/Zn-SOD immunoreactivity in the neurons and glial cells in both the striatum and substantia nigra after MPTP treatment. These results indicated that the ACE inhibitor perindopril can protect against MPTP-induced striatal dopamine and DOPAC depletion in mice. The protective effect may be, at least in part, caused by the reduction of free radicals caused by MPTP. The present study also demonstrated that perindopril is effective against MPTP-induced neurodegeneration of the nigro-striatal dopaminergic pathway. Furthermore, our results provided further evidence that free radical scavengers may be effective in the treatment of neurodegenerative diseases such as Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

First-line treatment in hypertension. Role of perindopril.

Once-daily administration of perindopril 4mg has been compared with captopril 25mg twice daily, atenolol 50mg once daily or a combination of hydrochlorothiazide 50mg plus amiloride 5mg once daily in double-blind studies of patients with supine diastolic blood pressures between 95 and 125mm Hg. After 3 months' treatment, the average decrease in supine systolic blood pressure with perindopril (26.5mm Hg) was significantly greater than that obtained with captopril (18.9mm Hg) and atenolol (20.6mm Hg), and non-significantly different from that achieved with the diuretic combination (30.6mm Hg). Perindopril reduced diastolic blood pressure by a greater extent than captopril (18.1 vs 11.7mm Hg), whereas the reductions were similar when compared with atenolol (17.4 vs 15.6mm Hg) and the diuretics (19.1 vs 18.4mm Hg). Target blood pressure (supine diastolic less than or equal to 90mm Hg) was achieved in 49 to 72% of patients on perindopril 4 mg/day and in an additional 15% of patients by doubling the dosage. In patients on perindopril who required an additional antihypertensive agent, a diuretic was more effective than a beta-blocker. Withdrawal rates due to adverse effects were similar in all treatment groups and ranged between 4 and 6%. Perindopril was well tolerated. In conclusion, these studies demonstrate that perindopril may be considered as a suitable first-line treatment for mild to moderate hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

[Effects of perindopril on plasma soluble TRAIL and receptor soluble DR5 in patients with congestive heart failure].

AIM: To explore the levels of soluble TRAIL and DR5 in plasma of patients with congestive heart failure (CHF) and the effects of perindopril. METHODS: 58 CHF patients were randomly divided into two groups, namely perindopril treatment group (30 cases) and routine treatment group (28 cases). The levels of sTRAIL and sDR5 in plasma of 30 CHF patients treated with perindopril, 28 CHF patients treated with routine method before and after treatment and 20 healthy persons were detected by ELISA. RESULTS: (1)The mean levels of sTRAIL in plasma of 58 CHF patients and 20 healthy persons were (1.43+/-0.47) microg/L and (0.93+/-0.12) microg/L, respectively, the comparison between the patients and healthy persons had no notable difference (P>0.05), suggesting that plasma sTRAIL level had no significant relation to injured level of cardiac function. As for sDR5 level, the mean level in plasma of 58 CHF patients was (39.67+/-6.78) ng/L, this value was significantly higher than that of healthy control group, and the level of sDR5 was increased with the injured level of cardic function.(2)The plasma levels of sTRAIL in both perindopril group and conventional treatment group decreased after treatment, but there was no significant difference. The mean levels of plasma sDR5 in perindopril group were (31.23+/-10.16 ) ng/L and (8.50+/-2.14) ng/L; the levels in conventional group (48.81+/-8.74) ng/L and (26.64+/-6.27) ng/L, respectively, the perindopril group was lower than the conventional group descending rates were 72.7% and 45.3% respectively.(3)The level of plasma sDR5 in CHF patients resulting from hypertensive cardiopathy was much higher than that in CHF patients resulting from any other etiological factors. CONCLUSION: DR5 may play an important role in the occurrence and progress of myocardium apoptosis of CHF patients. Perindopril can down-regulate the level of plasma sDR5, therefore, it may have the great effect on retarding course of ventricular remodeling, protecting and improving cardial function of CHF patients.

Apoptosis↗
PubMed1989

High affinity binding sites for Perindopril a new inhibitor of angiotensin-I-converting enzyme (ACE) in the rabbit kidney: possible evidence for localization of ACE in endothelial structures and in glomerular mesangium.

The tissue distribution of Perindopril, a new potent inhibitor of the angiotensin-converting enzyme (ACE), was studied after in vivo intravenous injection into rabbits of tracer amounts of the tritiated drug either alone (no modification of the renin angiotensin system) or along with a pharmacologic dose of 10 mg/kg unlabelled Perindopril. Lung and kidneys were the most densely labelled tissues. Kidney distribution of tritiated Perindopril was studied either by histo-autoradiography or by measurement of radioactivity in the homogenates of dissected kidney zones. A close parallelism was found between the distribution patterns of ACE and radioactivity throughout the kidney. Tritiated-Perindopril binding was inhibited by concurrent treatment of the animals with the unlabelled drug or pretreatment with Captopril. Autoradiographic study of kidney slices after the administration of tracer amounts of Perindopril showed an intense labelling of the glomerular mesangium and of endothelial structures of blood vessels, and a lack of labelling of tubular epithelial cells. The possible occurrence of two pools of "ACE-like" activity in the kidney is discussed, namely i) one pool which is labelled by tritiated Perindopril, located in glomerular mesangium and endothelial structures which may be involved in the pharmacological action of ACE inhibitors; and ii) a second pool located in the proximal-tubule cell brush-border, remaining unlabelled by Perindopril, for which the high amount of neutral endopeptidase present at this site may be responsible.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

[Hemodynamic effects of perindopril].

1. The effects of prolonged infusion of perindopril (1 mg/kg/d) were studied on Goldblatt rats and spontaneously hypertensive SHR rats compared to control animals. Perindopril increased significantly the arterial compliance in treated animals. Mechanical parameters of the carotid artery are normalized with perindopril infusion in renovascular hypertensive rats and improved in SHR rats. Perindopril reversed the thickness of aortic media in treated rats. After three months treatment the ratio elastine/collagen of the aortic media increased significantly. Perindopril reversed the majority of vascular alteration in both hypertensive groups. 2. Twenty one hypertensive patients received for 30 minutes an infusion of perindoprilat either at 1 mg/kg/min, or at 2.5 mg/kg/min, or dihydralazine at 4 mg/kg/min. It was shown that perindoprilat significantly reduced the blood pressure in the three groups. However the increase in arterial diameter and compliance were only recorded with perindoprilat (2.5 mg/kg/min) infusion. The results of this study pointed out that for the same antihypertensive effect, with two different antihypertensive drugs, the vascular effects can be different. Blood pressure, forearm hemodynamic parameters, echocardiography values were recorded on 16 sustained hypertensive patients before and after one year of perindopril treatment. The results showed that perindopril decreased significantly the SBP, DBP and the MBP, increased diameter and arterial compliance of the brachial artery, and decreased cardiac mass. Three months later, the treatment was stopped for four weeks: blood pressure and hemodynamic values returned toward basal values, whereas mass cardiac didn't increase significantly; then the treatment was continued over 9 months; during this period. The arterial compliance increased again on the cardiac mass remained reduced. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Captopril versus perindopril: a double blind study in essential hypertension.

This was a double blind, parallel group, multicentre comparison of the therapeutic efficacy and acceptability of perindopril and captopril in essential hypertension. After one month of placebo, 165 patients with supine diastolic blood pressure (DBP) between 95 and 125 mmHg were randomised to perindopril 4 mg once daily or captopril 25 mg twice daily orally. The perindopril group (n = 82) had significantly higher pretreatment DBP (105.4 +/- 0.8 mmHg vs 102.3 +/- 0.6 mmHg) but other demographic variables were similar. Assessment was monthly for three months: 'uncontrolled' patients (DBP greater than 90 mmHg) had the dose doubled and then hydrochlorothiazide added. Two of the six withdrawals were attributed to drug side effects and were in the captopril group. There was no significant difference in the number of withdrawals or incidence of side effects between the drugs. The final titrated treatments were similar and monotherapy normalised DBP in 49% of each group. The final 'control' rate was higher with perindopril than captopril: 75% vs 57%, P = 0.016. The overall fall in DBP was greater in the perindopril group: 26.5 +/- 1.9 mmHg vs 18.9 +/- 1.9 mmHg, P = 0.005. The doses of diuretic were similar in the two groups. The DBP of patients who received only monotherapy for three months also fell more in the perindopril group (-17.5 +/- 1.4 mmHg vs -13.9 +/- 1.0 mmHg, P less than 0.01). At the doses studied, perindopril was more effective than captopril in lowering DBP, either as monotherapy or in combination with a diuretic.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗