In order to evaluate the hypotensive effect of the lisinopril, a long acting angiotensin converting enzyme inhibitor, 10 to 30mg of lisinopril were administered in 35 hypertensive Korean adults during six weeks after a week observation for washout with stepwise increments of the dose according to the response of the patients blood pressure in every two weeks. The results were ; 1) The supine blood pressures were decreased from 163.7+/-16.6/99.8+/-9.3mmHg to 140.7+/-15.5/87.4+/-9.9mmHg at the end of six weeks' drug therapy(p<0.001). The standing blood pressures were also decreased conferrably and to the some lower levels. 2) In 14 patients to whom the drug was administered longer period(12 to 28 weeks) the blood pressure lowering effects were maintained at the level of that of 6th week. 3) Hematologic examination and blood chemistry revealed no discernible abnormal findings before and after the treatment. 4) In those patients who showed no adequate blood pressure control with other classes of antihypertensive drugs the lisinopril was effective in lowering their blood pressures by adding small doses. 5) During the period of the study a few probably drug-related symptoms developed but not troublesome except dry cough and dry mouth shich forced to stop administering the drug after completion of six weeks' period in one patients. From above results we concluded that lisnopril is effective and safe for the treatment of hypertension in Korean adults.
Adult ; Antihypertensive Agents ; Blood Pressure ; Chemistry ; Cough ; Humans ; Hypertension ; Lisinopril* ; Mouth ; Peptidyl-Dipeptidase A

BACKGROUND: The hypotensive effect of the lisinopril, a long acting angiotensin converting enzyme inhibitor, was studied. METHOD: 10mg of lisinopril was administered in 30 hypertensive Korean adults during twelve week after a weeks observation for washout with stepwise increments of the dose according to the patients blood pressure in every two weeks. RESULTS: The supine blood pressures were decreased from 173.3+/-27.9/105.7+/-19.4mmHg to 131.8+/-23.1mmHg/81.4+/-18.7mmHg at the end of twelve weeks durg therapy(P<0.05). The standing blood pressures were also decreased conferrably and to the some lower levels. Hematologic examination and blood chemistry revealed no discernible abnormal findings before and after the treatment. During the period of the study a few probably drug-related symptom such as dry cough and dry mouth developed but not troublesome enough to stop administering. CONCLUSION: Lisinopril 10mg once daily regimen is well tolerated and effective in the treatment of hypertensive patients.
Adult ; Blood Pressure ; Chemistry ; Cough ; Humans ; Hypertension ; Lisinopril* ; Mouth ; Peptidyl-Dipeptidase A

Angiotensin converting enzyme (ACE, EC 3.4.15.1) is a membrane-bound, zinc dependent dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the potent vasopressor ocatapeptide angiotensin II, by removing two C-terminal amino acids. ACE is well known as a key part of the renin angiotenisn system that regulates blood pressure, and its inhibitors have potential for the treatment of hypertension. This paper reviewed the characteristics of ACE in aspects of its structure-function relationship, gene polymorphism and inhibitor development. In particular, the catalytic mechanisms of the two active sites of somatic ACE in the cleavage of angiotensin I and bradykin are different. Therefore, it would likely provide a new way for exploiting novel ACE inhibitors with fewer side-effects by specifically-targeting the individual active sites of somatic ACE.
Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Antihypertensive Agents ; pharmacology ; Humans ; Peptidyl-Dipeptidase A ; chemistry ; genetics ; metabolism ; Polymorphism, Genetic ; Structure-Activity Relationship

Angiotensin I-converting enzyme (ACE) inhibitory peptides have been shown to have antihypertensive effects and have been utilized for physiologically functional foods and pharmaceuticals. The ACE inhibitory ability of a hydrolysate is determined by its peptide composition. However, the peptide composition of a hydrolysate depends on proteolytic enzyme and the hydrolysis conditions. In this study, the effect of process conditions on the ACE inhibitory activity of rice dregs hydrolyzed with a trypsin was investigated systematically using response surface methodology. It was shown that the ACE inhibitory activity of rice dregs hydrolysates could be controlled by regulation of five process conditions. Hydrolysis conditions for optimal ACE inhibition were defined using the response surface model of fractional factorial design (FFD), steepest ascent design, and central composite design (CCD).
Angiotensin-Converting Enzyme Inhibitors ; analysis ; chemistry ; Combinatorial Chemistry Techniques ; methods ; Drug Evaluation, Preclinical ; Enzyme Activation ; Hydrolysis ; Oryza ; chemistry ; Peptidyl-Dipeptidase A ; chemistry ; Plant Extracts ; chemistry ; Plant Proteins ; chemistry ; Protein Hydrolysates ; chemistry

BACKGROUND: In order to investigate the efficacy and safety of cilazapril, a recently developed angiotensin converting enzyme inhibitor, a clinical study was performed in the patients with mild to moderate essential hypertension. METHODS: The study subject consisted of 31 patients with diastolic blood pressure of 95mmHg~115mmHg (mean age : 56.0+/-8.1 years, 16 males and 15 females). Cilazapril was administered orally in a daily dose of 2.5mg~5.0mg Q.D. for 8 weeks. During cilazapril medication, anti-hypertensive efficacy, side effects and laboratory changes were monitored. RESULTS: Cilazapril decreased blood pressure from baseline value of 162.2+/-4.7/98.4+/-2.8mmHg to 144.6+/-10.0/89.7+/-5.7mmHg after 4weeks of medication (p<0.05) and 138.2+/-4.5/87.8+/-4.0mmHg after 8 weeks of medication (p<0.05). Heart rate change was not significant (72.3+/-4.7/min vs 71.7+/-3.6/min). Body weight change was not significant (66.6+/-9.8 Kg vs 66.8+/-9.9 Kg). There were no significant change in blood chemistry and hematologic examination except mild elevation of alanine transaminase and serum creatinine values but these date were within normal ranges. The side effects were dry cough (4 case, 12.9%), headache (2 case, 6.4%), indigestion (1 case, 3.2%) and dry mouth (1 case, 3.2%). One patient dropped out due to severe dry cough but others were mostly mild in nature. CONCLUSIONS: Cliazapril 2.5mg~5.0mg once daily regimen was effective and well tolerated in patients with mild to moderate essential hypertension.
Alanine Transaminase ; Blood Pressure ; Body Weight Changes ; Chemistry ; Cilazapril* ; Cough ; Creatinine ; Dyspepsia ; Headache ; Heart Rate ; Humans ; Hypertension* ; Male ; Mouth ; Peptidyl-Dipeptidase A ; Reference Values

BACKGROUND: The angiotensin-converting enzyme inhibitors have been found to be safe and efficacious in the treatment of essential hypertension. Fosinopril is the first angiotensin-converting enzyme inhibitor from a new class of agents containing phosphorus. This drug is known to be metabolized to almost and equal extent by the hepatic and renal pathways. METHODS: This study was performed to investigate the efficacy and safety of oral fosinopril, a new class of phosporus-containing angiotensin converting enzyme inhibitor, on essential hypertension. A single daily dose of 10mg to 20mg fosinopril was administered in 21 hypertensive patients with diastolic blood pressure in the range of 95mmHg-115mmHg while off all other anti-hypertensive agents for 10 weeks. Blood pressure and heart rate were measured every 4 weeks. The complete blood count, blood chemistry by SMA-12, serum electrolytes and urinalysis were performed at 12th week of therapy. RESULTS: 1) Baseline systolic and diastolic blood pressures after 2 weeks of placebo at sitting position were 158.8+/-15.7 and 99.4+/-6.3mmHg respectively. There was a statistcally significant reduction of blood pressure after 4 week treatment of fosinopril which was maintained up to 12 weeks of follow-up(158.8+/-15.7-99.4+/-6.3mmHg vs 139.3+/-18.2/86.6+/-10.3mmHg, p<0.05). 2) The proportion of responders defined by diastolic blood pressures less than 90mmHg or decline more than 10mmHg at 4, 8 and 12 weeks after treatment with fosinopril were 90.5, 95.2, and 95.2% respectively. 3) THere were no significant changes in blood chemistry, serum electrolytes, hematologic findings and heart rate over the treatment period. 4) Three patients experienced severe non-productive cough that required to discontinue the medication. CONCLUSION: In patients with mild to moderate hypertension, once-daily fosinopril(10mg and 20mg) provided significant anti-hypertensive effects without serious side effects. The 10mg dose was effective in majority of patients and may be considered as a starting dose.
Angiotensin-Converting Enzyme Inhibitors ; Antihypertensive Agents ; Blood Cell Count ; Blood Pressure ; Chemistry ; Cough ; Electrolytes ; Fosinopril* ; Heart Rate ; Humans ; Hypertension ; Peptidyl-Dipeptidase A ; Phosphorus ; Urinalysis

BACKGROUND AND OBJECTIVES: Angiotensin converting enzyme inhibitor (ACEI) is known to be effective in the prevention of left ventricular failure (LVF) after acute myocardial infarction. The aim of this study was to investigate the efficacy of an ACEI, Cilazapril, on left ventricular remodeling in patients with ischemic LVF, who underwent coronary interventions. MATERIALS AND METHODS: Cilazapril, 2.5 - 5.0 mg per day was administ-ered 12 weeks after coronary interventions in 25 patients (18 M, 7 F, 61.5+/-9 years) with impaired LV function (ejection fraction< or = 50%). Fifteen patients (9 M, 6 F, 59.4+/-7 years) without ACEI were compared by clinical examinations, blood chemistry, electrocardiogram and echocardiogram with Cilzapril group at 2, 4, 8 and 12 weeks after intervention. RESULTS: Blood pressure and heart rate were not changed after Cilazapril. LV end-diastolic volume (LVEDV) decreased from 153.1+/-38.7 to 135.6+/-25.5 ml and end-systolic volume from 84.9+/-34.7 to 72.6+/-25.1 ml after 12-week Cilazapril p=0.003, p=0.001. Ejection fraction (EF) was increased from 44.4+/-3.2 to 52.4+/-2.8% after 12 weeks of Cilazapril p=0.034. In control group, LVEDV was changed from 152.7+/-44.6 to 143.6+/-28.7 ml, which failed to show significant reduction. Side effects of Cilazapril were 3 dry cough (3/25, 12%) and 1 facial edema, 1 hypotension and 1 dizziness. CONCLUSION: Cilazapril is a beneficial adjunctive therapeutic agent in patients with ischemic left ventricular failure for the prevention of ventricular dilatation, especially after coronary intervention.
Blood Pressure ; Chemistry ; Cilazapril* ; Cough ; Dilatation ; Dizziness ; Edema ; Electrocardiography ; Heart Failure* ; Heart Rate ; Heart* ; Humans ; Hypotension ; Myocardial Infarction ; Peptidyl-Dipeptidase A ; Ventricular Remodeling*

In order to investigate the efficacy and safety of oral fosinopril, a new phosphorus containing angiotensin converting enzyme inhibitor, a single dose of 10 to 20mg was administered in 23 hypertensive patients with diastotic blood pressure above 95mmHg and all other anti-hypertensive agents were not administered during 4 weeks of study. Blood pressure and heart rate were measured on the 2nd and 4th week of therapy. The complete blood count with platelet count, blood chemistry by SMA-12 and serum electrolytes were performed at the begining and 4th week of therapy. The urinalysis and electrocardiography were performed at the beginning and 4th week of therapy. Any kinds of side effects were actively questioned by the examining physicians. The following results were obtained : 1) At the beginning and 4th weeks of therapy, the average systolic and diastolic pressure were 170.0+/-17.6/101.6+/-6.1mmHg, 142.7+/-15.1/87.3+/-6.7mmHg respectively. The systolic and diastolic blood pressure were declined statistically significantly(p<0.05) throughout the period of treatment and diastolic blood pressure of all subjects except 3 patients(86%) was maintained below 90mmHg after 4th week of treatment. 2) There was no significant change in the pulse rate before and after therapy. 3) There were no significant changes in blood chemistry, serum electrolytes, hematologic findings, urinalysis and electrocardiographic findigns. 4) side effect were developed in 5 patients(23%) with dry cough, 3 patients(13%) with headache and 2 patients with facial edema but side effects were mostly mild in nature without potenitally serious episodes. These results suggested that antihypertensive therapy with onec-daily fosinopril was effective and well tolerated in essential hypertensive patients.
Antihypertensive Agents ; Blood Cell Count ; Blood Pressure ; Chemistry ; Cough ; Edema ; Electrocardiography ; Electrolytes ; Fosinopril* ; Headache ; Heart Rate ; Humans ; Hypertension ; Peptidyl-Dipeptidase A ; Phosphorus ; Platelet Count ; Urinalysis

OBJECTIVETo screen angiotensin converting enzyme inhibitor (ACEI) from traditional Chinese medicine, Salvia miltiorrhiza.

METHODHydrophilic and lipophilic fractions of S. miltiorrhiza were isolated, and their effective components were screened by a fluorimetric assay for inhibition of angiotensin converting enzyme (ACE).

RESULTWater-soluble fractions, total salvianolic acids and salvianolic acid B markedly decreased ACE activity of rabbit lung tissue. Their IC50 value were (2.45 +/- 0.07), (0.24 +/- 0.02), (0.02 +/- 0.01) g x L(-1) respectively. Lipophilic components or phenanthraquinones including tanshinone I and II showed no changes on the activity of ACE.

CONCLUSIONS. miltiorrhiza inhibits angiotensin converting enzyme and its active components are in aqueous extract, in which the main were salvianolic acids including salvianolic acids B.

Angiotensin-Converting Enzyme Inhibitors ; isolation & purification ; pharmacology ; Animals ; Benzofurans ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; In Vitro Techniques ; Lung ; metabolism ; Peptidyl-Dipeptidase A ; metabolism ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Rabbits ; Rats ; Salvia miltiorrhiza ; chemistry

To find anti-hypertensive lead drug, angiotensin converting enzyme (ACE) inhibitory peptides were synthesized and their effects on inhibiting ACE activity were investigated. ACE inhibitory peptides were synthesized via Fmoc solid-phase synthesis, isolated and purified through reversed phase high-performance liquid chromatography (RP-HPLC), and identified by mass spectrometry. A RP-HPLC analysis method was used to test ACE inhibitory activity in vitro of these ACE inhibitory peptides. Six octapeptides were successfully synthesized, and the analytical results of mass spectrum were consistent with their theoretically calculated data. Among these synthetic octapeptides, the anti-SARS (severe acute respiratory syndromes) octapeptide had the most obvious ACE inhibitory activity with an IC50 value of 3.4 x 10(-5) mol x L(-1). So octapeptide AVLQSGFR-OH (anti-SARS peptide) was found to be the strongest candidate for potential development as an anti-hypertensive drug and had the implication of further study.
Angiotensin-Converting Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Antihypertensive Agents ; chemical synthesis ; chemistry ; pharmacology ; Chromatography, High Pressure Liquid ; methods ; Mass Spectrometry ; Molecular Structure ; Oligopeptides ; chemical synthesis ; chemistry ; pharmacology ; Peptidyl-Dipeptidase A ; drug effects ; Solid-Phase Synthesis Techniques