In the present study, the correlated activities of adjacent ganglion cells of transient subtype in response to full-field white light stimulation were investigated in the chicken retina. Pharmacological studies and cross-correlation analysis demonstrated that application of the GABA(A) receptor antagonist bicuculline (BIC) significantly down-regulated the correlation strength while increasing the firing activities. Meanwhile, application of the GABA(A) receptor agonist muscimol (MUS) potentiated the correlated activities while decreasing the firing rates. However, application of the GABA(C) receptor antagonist (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA) did not have a consistent influence on either the firing rates or the correlation strength. These results suggest that in the chicken retina, correlated activities among neighborhood transient ganglion cells can be increased while firing activities are reduced with the activation of GABA(A) receptors. The GABA(A)-receptor-mediated inhibitory pathway may be critical for improving the efficiency of visual information transmission.
Action Potentials ; Animals ; Bicuculline ; pharmacology ; GABA-A Receptor Antagonists ; pharmacology ; Mice ; Muscimol ; pharmacology ; Phosphinic Acids ; pharmacology ; Pyridines ; pharmacology ; Receptors, GABA-A ; metabolism ; Retina ; physiology ; Retinal Ganglion Cells ; physiology ; gamma-Aminobutyric Acid

No abstract available.
Fosinopril* ; Humans ; Hypertension*

BACKGROUND: This study was designed to evaluate the safety and the efficacy of fosinopril(Monopril(R)) in the treatment of mild to moderate essential hypertension. METHOD: Fosinopril(10mg) once a day was administrated as a starting dose in 20 patients with essential hypertension in the morning and a one step upward titration was performed(fosinopril 20mg once a day, after 4 weeks treatment). RESULT: After 2 weeks treatment with dose of 10mg, the systolic blood pressure(SBP) was decreased(183.8+/-28.5 vs, 161.5+/-25.9mmHg, p<0.05) and the diastolic blood pressure(DBP) was also decreased significantly(108.3+/-9.3 vs, 96.6+/-10.3mmHg, p<0.05). The effect of fosinopril were maintained. The SBP an DBP were decreased in 14 out of 20 patients till 8 weeks. There was no significant change in heart rate before and after fosinopril treatment(74.3+/-10 vs, 76.4+/-7.9beats/min). Fosinopril had no significant effects on laboratory findings such as serum creatinin, BUN, AST/ALT, WBC, Platelet and lipid profiles. Mild dry coughing was noticed only in 5 patients and it did not disturb continuing medication. CONCLUSION: Fosinopril is an effective antihypertensive agent, as monotherapy once a day in patients with mild to moderate hypertension.
Blood Platelets ; Cough ; Fosinopril* ; Heart Rate ; Humans ; Hypertension*

BACKGROUND: Losartan potassium, an orally active, highly selective AT (1) angiotensin II receptor inhibitor, effectively reduces blood pressure by directly blocking receptors. The purpose of this study is to compare the antihypertensive efficacy, safety and tolerability of losartan potassium and fosinopril in patients with stage 1 to 3 hypertnesion. METHODS: In this comparative, open labelled, randomized, parallel study, the efficacy, safety and tolerability of once-daily losartan (50mg) versus once-daily fosinopril (10mg) were evaluated over twelve weeks in 96 patients with stage 1-3 hypertension. If trough sitting diastolic blood pressure was equal to or greater than 90mmHg after a 6 week treatment period, the dosage for both study drugs was doubled until the end of the study (week 12). RESULTS: After 6 weeks of treatment, mean reductions in trough sitting diastolic blood pressure were 7.4mmHg (95% confidence interval 5.0-9.9) with 50mg losartan and 6.7mmHg (95% confidence interval 4.4-9.2)with 10mg fosinopril. After 12 weeks of treatment (after dose titration), mean reductions in trough sitting diastolic blood pressure were 9.4mmHg (95% confidence interval 6.7-12.1) with losartan and 10.3mmHg (95% confidence interval 7.6-12.9) with fosinopril. At weeks 6 and 12, there were no dignificant difference in the mean reduction of through ditting diastolic blood pressure between the losartan group and the fosinopril group. Losartan and fosinopril were well tolerated without significant clinical and laboratory adverse reactions. The incidence of dry cough was lower in the losartan group than in the fosinopril group but not statistically significant. CONCLUSIONS: The antihypertensive effect of once-daily administration of losartan is similar to that of once-daily administration of fosinopril in patients with hypertension. Both losartan and fosinopril are well tolerated without significant adverse reaction.
Blood Pressure ; Cough ; Fosinopril* ; Humans ; Hypertension* ; Incidence ; Losartan* ; Receptors, Angiotensin

BACKGROUND: The efficacy of oral angiotensin converting enzyme(ACE) inhibitors in the treatment of hypertension has been well documented. Fosinopril is a member of a new class of phosphorous containing ACE inhibitors and is a cleared almost equally by both renal and hepatic routes. METHODS: To evaluate the effects of fosinopril, a new angiotensin converting enzyme inhibitors, in patients with mild to moderate essential hypertension, we administered fosinopril 10~40mg/day once daily to 32 patients(14 males, 18 females; range of age, 40~71 years old) with dose titration every 2 weeks. RESULTS: The baseline blood pressure after 4 weeks wash-out period was 156.3+/-22.3/104.8+/-5.93mmHg. After fosinopril therapy, the blood pressure declined to 150.0+/-27.8/96.4+/-12.2mmHg with 10mmg/day and 144.4+/-20.0/95.21+/-9.95mmHg with 20mg/day, 139.6+/-18.3/85.1+/-9.71mmHg with 30mg/day.During the period of maintenance after dose titration of fosinopril every 2 weeks for 8 weeks, the blood pressure were declined statistically significant (p<0.05). But the heart rate was not changed throughout the period of treatment. The efficacy of fosinopril therapy disclosed 26 patients(81.3%) with normalized diastolic blood pressure and 4 patients(11.8%) with more than 10mmHg decline of diastolic blood pressure. Therefore, the efficacy of fosinopril in these particular patients was 93.1% and two patients(6.9%) showed a failure of fosinopril therapy. The adverse reaction due to fosinopril were reported in 3 patients(9.4%) with dry cough, 1 patients(3.1%) with palpitation and 1 patients(3.1%) with dizziness, but there were patients who discontinued fosinopril due to adverse reaction. CONCLUSION: These results suggested that antihypertensive therapy with fosinopril was effective and well tolerated in patients with mild to moderate essential hypertension.
Angiotensin-Converting Enzyme Inhibitors ; Angiotensins ; Blood Pressure ; Cough ; Dizziness ; Female ; Fosinopril* ; Heart Rate ; Humans ; Hypertension* ; Male

BACKGROUND: Fosinopril is a new phosphorous containing angiotensin converting enzyme inhibitor. To assess the antihypertensive efficacy and safety of fosinopril, the clinical trial was done in patients with mild to moderate hypertension. METHODS: In 30 patients with mild to moderate essential hypertension, we administered fosinopril 10-20mg once daily for 10 weeks and checked their blood pressure every 2 weeks. RESULTS: The blood pressure decreased from 158+/-12.3/103.4+/-4.2mmHg to 139+/-7.5/88.4+/-5.9mmHg at the end of treatment(p<0.05). Heart rate did not change significantly during therapeutic period. Of 30 patients, the efficacy of fosinopril therapy disclosed 25 patients(83.7%) with normal diastolic pressure of more than 10mmHg decline of diastolic blood pressure. But two patients had no effects and three patients were not followed up. The adverse reactions due to fosinopril were reported in 3 patients(10%) with dry cough, 2 patients with palpitation(6.7%) and 1 patient with weakness(3.3%), but there were no patients who discontinued fosinopril due to adverse effect. CONCLUSION: Fosinopril has an excellent antihypertensive effect at low dosage as a first line antihypertensive agent or as a substituting agent for other antihypertensives in patients with mild to moderate essential hypertension.
Antihypertensive Agents ; Blood Pressure ; Cough ; Fosinopril* ; Heart Rate ; Humans ; Hypertension ; Peptidyl-Dipeptidase A

BACKGROUND AND OBJECTIVES: Imidapril, one of the ACE inhibitor, has been used to treate hypertension, congestive heart failure, diabetes mellitus and renal disease. ACE inhibitor, however often causes dry cough and this adverse effect affects the compliance rate negatively. This report aimed to examine the incidence rate of coughing caused by Imidapril treat-ment. And we compared the results with the incidence and tendency of dry cough caused by the other ACE inhibitors. MATERIALS AND METHOD: This study enrolled 38 patients who followed up at internal medicine and took Imidapril from the period of May 9, 1997 to December 17, 1997. We tested its effectiveness, safety and tolerance. The initial dosage of it was 5mg/day and the maximum dosage according to blood pressure was 10mg/day for 8 weeks. The tendency and the incidence of dry cough have been analyzed and compared with recently published Korean reports. RESULTS: The 5 mg dosage of Imidapril showed 68.1% in lowering blood pressure rate and it went up to 81.8% during the 8 weeks treatment perriod. The blood pressure regularity rate was 36.3% after the 8 weeks treatment. The overall rate of adverse effect occurrence was 26.1% (6/23) and 8.7% of them were likely to cough. One of the patients who showed nausea stopped medication. The recent articles reported that the incidence of dry cough had been reduced: Enalapril (33.8%), Fosinopril (16%), Ramipril (15%), Imidapril (7.8 - 8.7%), Losartan (4.3%). CONCLUSION: Imidapril is as safe and effective as other ACE inhibitors. Various ACE inhibitors that were newly developed show their effectiveness in lessening incidence rate of dry cough, and Imidapril is thought to be an excellent drug for this matter. Even though Losartan shows the lowest incidence rate of dry cough, it needs to more regular usages since it is still on the stage of its medical adaptation.
Angiotensin-Converting Enzyme Inhibitors ; Angiotensins* ; Blood Pressure ; Compliance ; Cough* ; Diabetes Mellitus ; Enalapril ; Fosinopril ; Heart Failure ; Humans ; Hypertension ; Incidence* ; Internal Medicine ; Losartan ; Nausea ; Peptidyl-Dipeptidase A* ; Ramipril

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

OBJECTIVETo investigate the effect of fosinopril and metoprolol on metalloproteinases 9 (MMP9) expression of human umbilical vein endothelial cells (HUVECs) stimulated by oscillatory flow.

METHODSHUVECs were exposed to steady laminar flow or oscillatory flow, laminar flow or oscillatory flow plus various concentrations (1 x 10(-7) mol/L, 1 x 10(-5) mol/L) of fosinopril and metoprolol for 4 and 24 hours. MMP9 mRNA and protein expressions of HUVECs were determined by RT-PCR and Western blot, respectively.

RESULTSMMP9 expression at mRNA and protein levels were significantly increased in HUVECs exposed to oscillatory flow than that to laminar flow and these could be down-regulated by coincubation with fosinopril (1 x 10(-7) mol/L, 1 x 10(-5) mol/L, P < 0.01, P < 0.05, respectively) but not by co-incubation with metoprolol.

CONCLUSIONFosinopril can attenuate the increased MMP9 expression at mRNA and protein levels of HUVECs exposed to oscillatory flow.

Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; Endothelium, Vascular ; Fosinopril ; pharmacology ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Metoprolol ; pharmacology ; RNA, Messenger ; metabolism ; Stress, Mechanical ; Umbilical Veins ; cytology

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