경증 및 중등도 고혈압에서 Enalapril 의 강압 효과

김종성(Joug Seong Kim),강창운(Chang Woon Kang) 대한내과학회 1989 대한내과학회지 Vol.37 No.6

N/A A new antihypertensive agent, the angiotensin converting enzyme inhibitor enalapril 20 mg daily, was ad- ministered to 23 mild and 16 moderate hypertensive patients for 2 weeks or more. The combination of enalapril 20mg and hydrochlorothiazide 50mg daily was used in 3 mild and 16 moderate hypertensive patients without decreased BP and compared to enalapril alone 20 mg daily. CBC, urinalysis, serum chemistry, chest P-A and ECG were done before and after the treatment of enalapril. The results were as follows: 1) The standing systolic BP after the treatment of only enalapril 20 mg daily in 23 mild hypertensive patients was significantly decreased (142±8mmHg) compared with 179±12 mmHg before the treatment, and the supine systolic BP after the treatment was also significantly decreased (142±8 mmHg) compared with 181±10 mmHg before the treatment. The standing diastolic BP after the treatment of eualapril 20 mg daily was significantly decreased (78±7 mmHg) compared with 97±9mmHg before the treatment, and the supine diastolic BP after the treatment was significantly decreased (82±9mmHg) compared with 101±8 mmHg before the treatment. Enalapril alone (20 mg daily) decreased the BP to the normal limit in 20 (87%) of 23 mild hypertensive patients. 2) The standing systolic BP after the combined use of enalapril 20 mg and hydrochlorothiazide 50 mg daily in a totlal of 19 hypertensive patients; 3 mild and 16 moderate hypertensive patients without good response to enalapril alone, was significantly reduced (140±9 mmHg) compared with 188 mmHg before the treatment. Also the supine systolic BP after the combined use was significantly reduced (144±10 mmHg) compared with 186±13 mmHg before the treatment. The standing diastolic BP of 83±9 mmHg after the combined use of enalapril 20mg and hydrochlorothi-azide 50 mg daily in 19 hypertensive patients was significantly reduced compared with 101±13 mmHg before the treatment, and the supine diastolic BP of 85±8mmHg was also significantly reduced compared with 103±11 mmHg before the treatment. The combined use of enalapril 20 mg and hydrochlor-othiazide 50 mg daily decreased the RP to the normal range in 16 (84%) of 19 hypertensive patients without good response to enalapril alone 20 mg daily. 3) The heart rates were not significantly changed after the treatment of enalapril in 39 hypertensive patients. 4) The ECG findings in 39 hypertensive patients revealed ST-T wave changes in 9, LVH in 3, right B.B. B. in 2 and arrhythmia in 1 before the treatment of enalapril, and those persisted after the treatment. 5) The CBC, urinalysis and serum chemistry revealed normal ranges before and after the treatment of enalapril in 39 hypertensive patients. Chest P-A films in 39 hypertensive patients showed cardiomegaly in 4 before the treatment of enalapri l and the finding persisted after the treatment. 6) The adverse effects showed headache in 2, and dizziness and facial flushing in 1 each respectively of 39 hypertensive patients after the treatment of enalapril.

Comparison of Enalapril Maleate Tablets on Bioavailability and the Time Course of Inhibition of Plasma Angiotensin-Converting Enzyme

장인진,장병수,신상구,신재국,노일근,이경훈,박찬웅,Jang, In-Jin,Jang, Byung-Soo,Shin, Sang-Goo,Shin, Jae-Gook,Rho, Il-Kun,Lee, Kyeong-Hun,Park, Chan-Woong The Korean Society of Pharmacology 1990 대한약리학잡지 Vol.26 No.2

국내 생산 enalapril maleate 10mg 제제 $(Beartec^{\circledR})$의 생물학적 동등성을 검토키위해, 원 제조원인 Merck사의 $Vasotec^{\circledR}$을 기준 제제로하여 12명의 건강한 남성지원자를 대상으로 10mg 1회 경구 투여 교차시험후 약동학적 성상, ACE활성억제의 경시적 변화 및 혈압 변동을 검토한 결과는 다음과 같다. 1. 혈장 enalapril 및 활성형 대사물인 enalaprilat의 생체이용율 지표들(AUC, Tmax 및 Cmax)의 평균치는 시험제제에서 enalapril의 최고 혈장농도 도달시간(Tmax)이 약 27%(0.21시간)지연되었을 뿐 타 지포는 대조제제에 대한 백분율 차이에 있어 ${\pm}20%$내외였다. 2. 혈장 enalapril및 enalaprilat의 생체 이용율 지표들은 분산 분석에 의해 두 제제간에 차이를 인지할 수 없었다. 3. 시험제제의 생체이용율 지표들은, 대조제제에 대한 백분율을 95% 신뢰구간 검정시, enalapril의 AUC 및 Tmax를 제외한 enalapril 및 enalaprilat의 모든 지표는 ${\pm}20%$ 내외의 결과를 보였다. 4. 두제제 투여후 ACE활성도는 enalaprilat 혈장농도 5-6ng/ml에서 50%의 억제를 보였으며, 투약 23시간까지의 활성억제 AUC는 차이가 없었다. 5. 두 제제 투여후 수축기 및 이완기 혈압은 투약 2시간 이후 유의한 감소를 보였으며 혈압 변동은 두제제간에 차이를 인지할 수 없었다. 이상의 실험 결과로 enalapril maleate의 국내 생산 generic product는 기준제제인 $Vasotec^{\circledR}$과 동등한 생물학적 동등성을 지니며 치료적 등가성을 보이는 제제로 판단하였다. Enalapril maleate tablets of two different producers were tested for bioequivalence. Enalapril is rapidly metabolized to an active metabolite, enalaprilat which inhibits angiotensin-converting enzyme (ACE). The pharmacokinetics of enalapril maleate and the time course of inhibition of plasma ACE activity after administration of the drugs were studied. Two single doses of 10mg each of enalapril maleate were administered orally to twelve male volunteers in a balanced, randomized, two-way crossover investigation. Plasma enalaprilat concentrations were determined over a 23-hour after the dose by enzyme inhibition assay and enalapril by the same method following in vitro hydrolysis. Urinary recoveries of enalapril and enalaprilat were determined for the calculation of renal clearance. Plasma ACE activity was determined by an enzyme assay. Peak plasma levels of enalapril were observed about 1 hour after the doses, and practically all enalapril had disappeared from plasma within 6 hour. Peak enalapril concentrations of both formulations were almost identical ($Vasotec^{\circledR}$, 61.38 ng/ml; $Beartec^{\circledR}$, 64.27 ng/ml). The values of the pharmacokinetic parameters of enalaprilat computed for $Vasotec^{\circledR}$ and $Beartec^{\circledR}$ tablets are presented in that order; area under the curve=330.63:320.96 $ng{\cdot}hr/ml$; peak concentration=38.63:39.43 ng/ml; time to peak=3.83:4.08 hour; elimination half-life=3.95:3.92 hours. No statistically significant difference was detected when area under the curve and all other parameters were compared. Using criteria of 95% confidence interval for the comparison of these parameters, only the upper limits of area under the curve and time to peak of enalapril were over 120%. All the parameters of enalaprilat were acceptable. Percent inhibition of plasma ACE to plasma enalaprilat concentration showed the sigmoid concentration-inhibition relationship. Time courses of plasma ACE inhibition after the administration of both formulations were quite similar. The formulations were found to be equivalent when compared on the premise that no significant difference was detected when pharmacokientic parameters and inhibition of ACE activity were compared, based on the confidence limits analysis.

Enalapril Maleate 정제의 동등성에 관한 연구 ; 약동학적 성상 및 혈장 ACE 활성도 억제 효과

장인진(In-Jin Jang),장병수(Byung-Soo Jang),신상구(Sang-Goo Shin),신재국(Jae-Gook Shin),노일근(Il-Kun Rho),이경훈(Kyeong Hun Lee),박찬웅(Chan Woong Park) 대한약리학회 1990 대한약리학잡지 Vol.26 No.2

국내 생산 enalapril maleate 10mg 제제 (Beartec^??)의 생물학적 동등성을 검토키위해, 원 제조원인 Merck사의 Vasotec^??을 기준 제제로하여 12명의 건강한 남성지원자를 대상으로 10mg 1회 경구 투여 교차시험후 약동학적 성상, ACE활성억제의 경시적 변화 및 혈압 변동을 검토한 결과는 다음과 같다. 1. 혈장 enalapril 및 활성형 대사물인 enalaprilat의 생체이용율 지표들(AUC, Tmax 및 Cmax)의 평균치는 시험제제에서 enalapril의 최고 혈장농도 도달시간(Tmax)이 약 27%(0.21시간)지연되었을 뿐 타 지포는 대조제제에 대한 백분율 차이에 있어 ± 20%내외였다. 2. 혈장 enalapril및 enalaprilat의 생체 이용율 지표들은 분산 분석에 의해 두 제제간에 차이를 인지할 수 없었다. 3. 시험제제의 생체이용율 지표들은, 대조제제에 대한 백분율을 95% 신뢰구간 검정시, enalapril의 AUC 및 Tmax를 제외한 enalapril 및 enalaprilat의 모든 지표는 ± 20% 내외의 결과를 보였다. 4. 두제제 투여후 ACE활성도는 enalaprilat 혈장농도 5-6ng/ml에서 50%의 억제를 보였으며, 투약 23시간까지의 활성억제 AUC는 차이가 없었다. 5. 두 제제 투여후 수축기 및 이완기 혈압은 투약 2시간 이후 유의한 감소를 보였으며 혈압 변동은 두제제간에 차이를 인지할 수 없었다. 이상의 실험 결과로 enalapril maleate의 국내 생산 generic product는 기준제제인 Vasotec^??과 동등한 생물학적 동등성을 지니며 치료적 등가성을 보이는 제제로 판단하였다. Enalapril maleate tablets of two different producers were tested for bioequivalence. Enalapril is rapidly metabolized to an active metabolite, enalaprilat which inhibits angiotensin-converting enzyme (ACE). The pharmacokinetics of enalapril maleate and the time course of inhibition of plasma ACE activity after administration of the drugs were studied. Two single doses of 10mg each of enalapril maleate were administered orally to twelve male volunteers in a balanced, randomized, two-way crossover investigation. Plasma enalaprilat concentrations were determined over a 23-hour after the dose by enzyme inhibition assay and enalapril by the same method following in vitro hydrolysis. Urinary recoveries of enalapril and enalaprilat were determined for the calculation of renal clearance. Plasma ACE activity was determined by an enzyme assay. Peak plasma levels of enalapril were observed about 1 hour after the doses, and practically all enalapril had disappeared from plasma within 6 hour. Peak enalapril concentrations of both formulations were almost identical (Vasotec^??, 61.38 ng/ml; Beartec^??, 64.27 ng/ml). The values of the pharmacokinetic parameters of enalaprilat computed for Vasotec^?? and Beartec^?? tablets are presented in that order; area under the curve=330.63:320.96 ng⋅hr/ml; peak concentration=38.63:39.43 ng/ml; time to peak=3.83:4.08 hour; elimination half-life=3.95:3.92 hours. No statistically significant difference was detected when area under the curve and all other parameters were compared. Using criteria of 95% confidence interval for the comparison of these parameters, only the upper limits of area under the curve and time to peak of enalapril were over 120%. All the parameters of enalaprilat were acceptable. Percent inhibition of plasma ACE to plasma enalaprilat concentration showed the sigmoid concentration-inhibition relationship. Time courses of plasma ACE inhibition after the administration of both formulations were quite similar. The formulations were found to be equivalent when compared on the premise that no significant difference was detected when pharmacokientic parameters and inhibition of ACE activity were compared, based on the confidence limits analysis. plasma ACE inhibition after the administration of both formulations were quite similar. The formulations were found to be equivalent when compared on the premise that no significant difference was detected when pharmacokientic parameters and inhibition of ACE activity were compared, based on the confidence limits analysis. plasma ACE inhibition after the administration of both formulations were quite similar. The formulations were found to be equivalent when compared on the premise that no significant difference was detected when pharmacokientic parameters and inhibition of ACE activity were compared, based on the confidence limits analysis.

1~2기 본태성 고혈압 환자들에서 Imidapril 대 Enalapril의 항고혈압 효과를 평가하기 위한 무작위, 이중맹검 임상시험

최영진,손대원,김용진,이홍자,채인호,김효수,김철호,오병희,이명묵,박영배,채윤식,이영우 대한순환기학회 1999 Korean Circulation Journal Vol.29 No.11

신증후군 환아에서 Enalapril의 단백뇨 감소 효과

이명숙,김향숙,박광준,손인자,이숙향 한국병원약사회 2001 병원약사회지 Vol.18 No.3

Enalapril, an angiotensin converting enzyme inhibitor, has been used to treat pediatric patients with nephrotic syndrome. The objective is to study the antiproteinuric effect of enalapril in children with nephrotic syndrome. Patients were eligible when children with nephrotic syndrome were treated with enalapril and corticosteroid at Seoul National University Children's Hospital. The exclusion criteria were the secondary nephrotic syndrome. Dosage of enalapril started with 0.1 ㎎/㎏/d. The primary variables evaluating efficacy of enalapril on nephrotic syndrome were time-dependent changes in serum total protein, albumin, total cholesterol and serum creatinine, BUN and ruinary protein/creatinine ratio. Adverse drug events associated with enalapril and corticosteroid were evaluated. There were total 35 patients with 26 boys and 9 girls, age ranging from 3 to 22 years. Ten patients had hypertension at baseline. Histological lesions were focal and segmental glomerulosclerosis in 18; minimal change nephrotic syndrome in 7; membranoproliferative glomerulonephritis in 2; membranous glomerulonephritis in 1 and 7 patients not done kidney biopsy. Serum total protein and albumin levels increased simultaneously. Total protein increased from 5.1(±1.1) g/dL to 5.7(±1.0) g/dL (p=0.029) and 6.1(±1.1) g/dL (p=0.009) at 6 months and 3 years after treatment, respectively. Serum albumin increased from 2.4(±0.9) g/dL to 2.9(±0.9) g/dL (p=0.009) and 3.3(±1.2) g/dL (p=0.005) at 6 months and 3 years after treatment, respectively. Total cholesterol level decreased from 384.7(±156.5) ㎎/dL to 293.4(±160.5) ㎎/dL (p=0.081) at 3 years after treatment. Serum. creatinine level showed statistically significant change and BUN level showed no statistically significant change. Enalapril treatment was associated with significant and persistent reduction of urinary protein/creatinine ratio from 16.3(±20.6) to 6.0(±8.9) (p=0.011) and 3.7(±7.0) (p=0.003) at 6 months 3 years after treatment, respectively. Side effects of enalapril were observed for cough in one patient and elevated BUN and Scr in one patient. We conclude that enalapril treatment was effective in reducing proteinuria with preserved renal funtion.

선천성 고혈압흰쥐에서 Endothelin과 Neuropeptide Y에 의한 심혈관계 반응에 Enalapril 장기처치가 미치는 영향

김권배(Kwon-Bae Kim),손의동(Uy-Dong Sohn),김중영(Choong Young Kim) 대한약리학회 1992 대한약리학잡지 Vol.28 No.1

선천성 고혈압 흰쥐(SHR)에서 endothelin-1(ET)과 neuropeptide Y(NPY) 투여에 의한 심혈관계 반응에 미치는 enallapril 장기처치의 영향을 검토하였다. 생후 6주의 SHR에 enalapril(3 mg/kg/day)을 6주간 투여하였을 때 고혈압 발현이 현저히 억제되었다(이하 enalapril 처치군). Enalapril 처치군에서 ET 및 NPY에 의한 승압반응이 현저히 억제되었지만, ET 측뇌실투여에 의한 혈압상승 및 NPY측뇌실 투여로 야기되는 혈압하강효과에는 영향이 없었다. 뇌척수제거 흰쥐에서 전기적 자극으로 야기되는 빈맥효과는 enalapril처치나 ET투여로 억제되었는데, ET의 작은 α₂-수용체 길항제인 yohimbine 전처치로 봉쇄되었다. SHR의 적출 대동맥에서 전기자극 빈도수에 따르는 수축반응이 ET 전처치로 항진되었으나 NPY 전처치로는 차이가 없었다. 전기자극 빈도수에 따른 수축반응은 enalapril투여한 군의 것이 투여하지 않은 군의 것에 비하여 약화되었다. ET투여에 의한 혈중 norepinephrine의 증가작용이 enalapril처치로 감소되었으며, 이러한 감소작용이 뇌척수제거 흰쥐에서 현저하였다. 위의 결과로 미루어 고혈압흰쥐에 enalapril을 장기처치함으로써 고혈압 발현을 효과적으로 억제할 수 있으며, 이는 ET 및 NPY에 의한 승압반응 및 교감신경말단의 신경전달과정의 억제가 관여될 수도 있을 것 같다. This study was designed to evaluate the responses of cardiovascular system to endothelin (ET) and neuropeptide Y (NPY) in 12 week-old SHR treated with or without enalapril (ENP) for 6 weeks. The diastolic blood pressure and heart rate were lower in ENP-treated SHR than in control. The pressor response to intravenous, but not intracerebroventricular, ET or NPY was attenuated by ENP treatment. The chronotropic action induced by electrical stimulation was attenuated by ENP or ET. The negative chronotropic action of ET was blocked by yohimbine. The increase in aortic tension induced by electrical field stimulation (EFS) was depressed in ENP-treated group as compared with non-treated group, and enhanced by ET, but not NPY, in the non-treated group. The ET-induced increase in tension was enhanced by removal of endothelium in the control group but not in ENP-treated group. The plasma concentration of norepinephrine and ET-induced increase in concentration of norepinephrine and epinephrine in plasma were decreased in ENP-treated group. These results suggest that preventive effect of enalapril on the development of hypertension may result from depressing vasoactive action of endothelin and neuropeptide Y, and sympathetic neurotransmission at peripheral nervous system.

Long-Term Treatment with Enalapril Depresses Endothelin and Neuropeptide Y-induced Vasoactive Action in Spontaneously Hypertensive Rats

김권배,손의동,김중영,Kim, Kwon-Bae,Sohn, Uy-Dong,Kim, Choong-Young The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.1

This study was designed to evaluate the responses of cardiovascular system to endothelin (ET) and neuropeptide Y (NPY) in 12 week-old SHR treated with or without enalapril (ENP) for 6 weeks. The diastolic blood pressure and heart rate were lower in ENP-treated SHR than in control. The pressor response to intravenous, but not intracerebroventricular, ET or NPY was attenuated by ENP treatment. The chronotropic action induced by electrical stimulation was attenuated by ENP or ET. The negative chronotropic action of ET was blocked by yohimbine. The increase in aortic tension induced by electrical field stimulation (EFS) was depressed in ENP-treated group as compared with non-treated group, and enhanced by ET, but not NPY, in the non-treated group. The ET-induced increase in tension was enhanced by removal of endothelium in the control group but not in ENP-treated group. The plasma concentration of norepinephrine and ET-induced increase in concentration of norepinephrine and epinephrine in plasma were decreased in ENP-treated group. These results suggest that preventive effect of enalapril on the development of hypertension may result from depressing vasoactive action of endothelin and neuropeptide Y, and sympathetic neurotransmission at peripheral nervous system. 선천성 고혈압 흰쥐(SHR)에서 endothelin-1(ET)과 neuropeptide Y(NPY) 투여에 의한 심혈관계 반응에 미치는 enallapril 장기처치의 영향을 검토하였다. 생후 6주의 SHR에 enalapril(3 mg/kg/day)을 6주간 투여하였을 때 고혈압 발현이 현저히 억제되었다(이하 enalapril 처치군). Enalapril 처치군에서 ET 및 NPY에 의한 승압반응이 현저히 억제되었지만, ET 측뇌실투여에 의한 혈압상승 및 NPY측뇌실 투여로 야기되는 혈압하강효과에는 영향이 없었다. 뇌척수제거 흰쥐에서 전기적 자극으로 야기되는 빈맥효과는 enalapril처치나 ET투여로 억제되었는데, ET의 작은 ${\alpha}_2$-수용체 길항제인 yohimbine 전처치로 봉쇄되었다. SHR의 적출 대동맥에서 전기자극 빈도수에 따르는 수축반응이 ET 전처치로 항진되었으나 NPY 전처치로는 차이가 없었다. 전기자극 빈도수에 따른 수축반응은 enalapril투여한 군의 것이 투여하지 않은 군의 것에 비하여 약화되었다. ET투여에 의한 혈중 norepinephrine의 증가작용이 enalapril처치로 감소되었으며, 이러한 감소작용이 뇌척수제거 흰쥐에서 현저하였다. 위의 결과로 미루어 고혈압흰쥐에 enalapril을 장기처치함으로써 고혈압 발현을 효과적으로 억제할 수 있으며, 이는 ET 및 NPY에 의한 승압반응 및 교감신경말단의 신경전달과정의 억제가 관여될 수도 있을 것 같다.

Effects of Angiotensin Converting Enzyme Inhibition on Gene Expression of the Renin-Angiotensin System in Rats

Young Rae Lee,Mi Young Lee,Woon Jung Kim,Won Jung Lee 대한생리학회-대한약리학회 1998 The Korean Journal of Physiology & Pharmacology Vol.2 No.6

<P> To investigate interaction of angiotensin converting enzyme (ACE) inhibitor with local tissue renin- angiotensin system (RAS), changes in gene expression of the RAS components in various tissues in response to chronic administration of an ACE inhibitor, enalapril, were examined in Sprague-Dawley male rats. Enalapril was administered in their drinking water (3∼4 mg/day) over 8 wk. Plasma and renal ACE activity increased significantly after 4 and 8 wk of enalapril treatment. Renin levels of the plasma and kidney of the enalapril-treated rats markedly increased after 4 wk and decreased thereafter, but still remained significantly higher than those of control rats. Kidney mRNA levels of renin markedly increased after 4 and 8 wk of enalapril treatment, but those of angiotensinogen and ANG II-receptor subtypes, AT<SUB>1A</SUB> and AT<SUB>1B</SUB>, did not change significantly. The liver expressed genes for renin, angiotensinogen and AT<SUB>1A</SUB> receptor subtype, but AT<SUB>1B</SUB> receptor subtype mRNA was not detectable by RT-PCR. None of mRNA for these RAS components in the liver changed significantly by enalapril treatment. The hypothalamus showed mRNA expressions of renin, angiotensinogen, AT<SUB>1A </SUB>and AT<SUB>1B</SUB> receptor subtypes. AT<SUB>1A</SUB> receptor subtype mRNA was more abundant than AT<SUB>1B</SUB> receptor subtype in the hypothalamus as shown in the kidney. However, gene expression of the RAS components remained unchanged during 8-wk treatment of enalapril. In the present study, chronic ACE inhibition increased plasma and renal levels of ACE and renin, but did not affect mRNA levels of other RAS components such as angiotensinogen, ANG II receptor subtypes in the kidney. Gene levels of the RAS components in the liver and hypothalamus were not altered by chronic treatment of enalapril. These results suggest the differential expression of the RAS components in response to enalapril, and localized action and some degree of tissue specificity of enalapril.

Comparison of Inhibitory Effects between Enalapril and Losartan on Adrenal Catecholamine Secretion

임효정,고영엽,임동윤 대한고혈압학회 2014 Clinical Hypertension Vol.20 No.2

Background: The present study was attempted to compare enalapril, an angiotensin-converting enzyme inhibitor withlosartan an angiotensin II (Ang II) receptor blocker in the inhibitory effects on the secretion of catecholamines (CA) fromthe perfused model of the rat adrenal gland. Methods: The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer. Results: Both enalapril and losartan during perfusion intoan adrenal vein for 90 minutes inhibited the CA release evoked by acetylcholine (ACh), 1.1-dimethyl-4-phenyl piperazinium(DMPP, a selective Nn agonist), high K+ (a direct membrane-depolarizer), 3-(m-chloro-phenyl-carbamoyl-oxy-2-butynyltrimethylammonium (McN-A-343, a selective M1 agonist), and Ang II in a time-dependent manner. Also, in the presence ofenalapril or losartan, the CA release evoked by veratridine (an activator of voltage-dependent Na+ channels),6-dimethyl-3-nitro-4-(2-trifluoromethyl–phenyl)-pyridine-5-carboxylate (BAY-K-8644, an L-type Ca2+ channel activator),and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor) were significantly reduced. Based on the same concentrationof enalapril and losartan, for the CA release evoked by ACh, high K+, DMPP, McN-A-343, Ang II, veratridine,BAY-K-8644, and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: losartan > enalapril. Inthe simultaneous presence of enalapril and losartan, ACh-evoked CA secretion was more strongly inhibited compared withthat of enalapril- or losartan-treated alone. Conclusions: Collectively, these results demonstrate that both enalapril andlosartan inhibit the CA secretion evoked by activation of both cholinergic and Ang II type-1 receptors stimulation in theperfused rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may alsobe of clinical benefit. Based on concentration used in this study, the inhibitory effect of losartan on the CA secretion seemsto be more potent than that of enalapril.

Enalapril 경구 투여가 혈중 Angiotensin 전환효소 활성도에 미치는 영향

유언호,류호준 중앙대학교 의과대학 의과학연구소 1995 中央醫大誌 Vol.20 No.1

Enalapril, a angiotensin converting enzyme(ACE) inhibitor, was given in a single oral dose of 10mg to 13 patients with essential hypertension and to 10 control patients with normal blood pressure. Blood pressure, plasma renin activity, aldosteron, and SCE activity were measured before and after enalapril administration. The results were as follow : 1. At 3 hours. after administration of enalapril, plasma ACE activity decreased in both groups of patients(p<0.05) but more decreased in patients with essential hypertension from 19.4±8.8 to 9.7±5.7 nmole/min/ml(p<0.05). 2. Decresed levels of plasma ACE activity were accompanied by reduction of blood pressure in response to enalapril, especially systolic blood pressure in patients with hypertension. Blood pressure also decreased in both groups of patients including those with normal or low renin levels(p<0.05), but there was not a significant correlation between the magnitude of blood pressure reduction and baseline plasma renin activity. 3. After 10mg of enalapril administration, mean plasma renin activity rose(p<0.05), while plasma aldosterone concentration fell in both groups of patients. It suggest that enalapril is an effective ACE inhibitor and the measurement of plasma ACE activity is useful for monitoring the efficacy of ACE inhibitor and compliance to treatment with enalapril.