OLETF쥐에서 Amlodipine, Losartan과 비교한 Lithospermic Acid B의 당뇨병성 신증 예방효과

강은석,하헌주,허규연,차봉수,김범석,김철훈,안철우,이현철,서기호,한승진,전성완,정만길 대한당뇨병학회 2008 Diabetes and Metabolism Journal Vol.32 No.1

Background: Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. Methods: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. Results: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β1 (TGF-β1). Conclusion: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan. (J Kor Diabetes Assoc 32:10~20, 2008) Background: Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. Methods: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. Results: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β1 (TGF-β1). Conclusion: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan. (J Kor Diabetes Assoc 32:10~20, 2008)

Angiotensin Ⅱ 수용체 선택적 길항제 Losartan이 Spontaneously Hypertensive Rat 적출 대동맥의 수축에 미치는 영향

김춘식,한형수,김중영 慶北大學校 醫科大學 1994 慶北醫大誌 Vol.35 No.4

목적 : SHR의 장간막을 적출하여 장간막 혈관 관류를 시켰을 때 losartan을 2주간 처치한 군에서 대조군에 비해 norepinephrine을 투여하여 나타나는 관류압의 상승에 대한 전기자극에 의한 관류압의 비가 감소되어 나타났다. 이러한 현상의 원인을 검정하고자 하였다. 대상 및 방법 : SHR의 적출 대동맥에 90분 동안 losartan을 처치하였을 때 처치전후에 phenylephrine과 KCl에 의한 수축력의 차이를 비교하였다. 결과 : losartan 처치로 수축력이 감소됨을 확인하였다. 또 내피세포를 가진 대동맥 절편이 내피를 제거한 절편보다 수축력의 감소가 더 현저하게 나타내었다. 한편 losartan에 의한 수축력 감소 현상은 2주간 ACEI인 enalapril을 식수에 타서 먹인 경우에는 나타나지 않았다. 결론 : losartan에 의해 KCl이나 phenylephrine에 의한 수축력이 감소하는 것은 혈관에 존재하는 RAS 특히 angiotensin Ⅱ의 다른 수축제의 작용을 증가시키는 작용이 차단됨에 따른 것임을 짐작할 수 있었다. 또 내피세포를 가진 대동맥 절편이 내피세포 제거한 절편에서보다 losartan에 의한 수축력 감소를 더 현저히 보이는 현상은 내피세포가 losartan의 영향을 받아 생긴 것으로 사료된다. The perfusion pressure ratio, electrical field stimulation(40 V, 5 msec, 40 ㎐, 30 sec)-induced pressure change/norepinephrine(10^-5M, 15 ㎖)-induced pressure change, in isolated mesenteric bed was evaluated. Losartan-treated (30 ㎎/㎏/day, 2 weeks) SHR showed decreased perfusion pressure ratio compared with control. To evaluate the cause of the decrease in perfusion pressure ratio we used isolated aorta. Incubation with losartan (10^-4M, 90 min) decreased the contractile response induced by phenylephrine(10^-7M) and KCI(50 mM) and the decreased response was not shown in enalapril treated(5 ㎎/㎏/day, 2 weeks) SHR. The decreased contractile response by losartan was more prominent in endothelium intact strip and less remarkable in denuded strip. From these results we can assume that losartan decreased the contractile response by eliminating local renin angiotensin system, particularly in the endothelium of aorta and therefore by reducing the contraction amplifying effect of angiotensin Ⅱ.

Simvastatin and Losartan Differentially and Synergistically Inhibit Atherosclerosis in Apolipoprotein E -/- Mice

이복수,Jin Yong Choi,Joo Yun Kim,Seul Hee Han,박정의 대한심장학회 2012 Korean Circulation Journal Vol.42 No.8

Background and Objectives: Since statins and angiotensin receptor blockers are a frequently prescribed combination in patients with atherosclerotic cardiovascular diseases, we tested the interactive effects of simvastatin and losartan on atherosclerosis in apolipoprotein E (apoE) -/- mice. Materials and Methods: Apolipoprotein E -/- mice were fed a high-fat, high-cholesterol (HFHC) diet for 12 weeks, with and without simv-astatin (40 mg/kg) and/or losartan (20 mg/kg). The mice were divided into 5 groups and were fed as follows: regular chow (control diet, n=5),HFHC diet (n=6), HFHC diet with losartan (n=6), HFHC diet with simvastatin (n=6), and HFHC diet with both losartan and simvastatin (n=6). Results: Losartan treatment in apoE -/- mice significantly decreased atherosclerotic lesion areas in whole aortic strips stained with Oil Red O. The plaque area measured at the aortic sinus level was reduced significantly by 17% (HFHC; 346830.9 ±52915.8 μm 2 vs. HFHC plus losar-tan; 255965.3±74057.7 μm 2 , p<0.05) in the losartan-treated group. Simvastatin and simvastatin plus losartan treatments reduced macro-phage infiltration into lesions by 33% (HFHC; 183575.6 ±43211.2 μm 2 vs. HFHC plus simvastatin; 120556.0±39282.8 μm 2 , p<0.05) and 44% (HFHC; 183575.6±43211.2 μm 2 vs. HFHC plus simvastatin and losartan; 103229.0±8473.3 μm 2 , p<0.001, respectively). In mice fed the HFHC diet alone, the smooth muscle cell layer in the aortic media was almost undetectable. In mice co-treated with losartan and simvas-tatin, the smooth muscle layer was more than 60% preserved (p<0.05). Given alone, losartan showed a slightly stronger effect than simv-astatin; however, treatment with losartan plus simvastatin induced a greater inhibitory effect on atherosclerosis than either drug given alone. Serum lipid profiles did not differ significantly among the groups. Conclusion: Losartan displayed anti-atherosclerotic effects in apoE -/- mice that were equivalent to or greater than the effects of simvas-tatin. Combined treatment with these drugs had greater effect than either drug alone.

Losartan이 Wistar-Kyoto Rat과 Sprague-Dawley Rat의 적출 대동맥 수축에 미치는 영향

김경재,한형수 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.4

목적 : Losartan을 적출대동맥에 처치하였을 때 phenylephrine과 KCI에 의한 수축반응의 감소가 일어난다고 하는데, 정상혈압 동물에서도 losartan이 수축력에 영향을 주는지 그리고 영향을 준다면 어떤 기전에 의해서 야기되는지를 검토 하고자 하였다. 대상 및 방법 : 생후 18주 이상된 정상혈압흰쥐 즉 SD와 WKY의 적출대동맥을 적출하여 90분간 losartan(10-5 M) 존재하에서 phenylephrin, KCI에 의한 수축반응과 histamine, nitroprusside에 의한 이완반응을 비교하였다. 결과 : Losartan을 90분동안 처치하면 phenylephrine과 KCI에 의한 수축 반응은 감소되었으나 phorbol ester에 의한 수축은 감소되지 않았다. 한편 losartan 존재하에서 nitric oxide synthase 억제제인 LNAME를 처치하면 수축력 감소가 나타나지 않았다. 그리고 histamine과 sodium nitroprusside에 의한 이완작용은 losartan 처치에 따른 영향을 받지 않았다. 결론 : 이상의 실험 결과에서 정상혈압에서도 losartan은 수축력 감소를 일으키며 이 작용은 protein kinase C 억제에 의한 것 같으며, losatan이 주로 basal release되는 nitric oxide에 영향을 주나, 외부자극에 의해 유리되는 nitric oxide와 cGMP에 의한 이완력에는 영향을 주지 않은 것으로 생각된다. It was aimed to evaluate the effect of losartan, angiotensin Ⅱ receptor blocker, on the contractile response of isolated aorta from normotensive rats, Sprague-Dawley and Wistar-Kyoto rats. Phenylephrine- and KCI-induced contractile responses were attenuated by losartan treatment(100 uM, for 90 min) but phorbol ester-induced contractile response was not attenuated. And in the presence of LNAMW(100 uM), attenuaton of phenylephrine-induced contractile response was not shown. Relaxing responses by histamine, endogenous nitric oxide releasing stimulator, and sodium nitroprusside, nitric oxide releaser, were not altered by losatan treatment. From these results it is suggested that losartan attenuates the contractile responses by inhibiting protein kinase C-mediated contraction and by enhancing basal release of nitric oxide.

실험적 급성 심근경색증 후 좌심실 재성형에 관여하는 간질 조직의 변화에 대한 전환효소억제제의 기전에 대한 연구 : 백서의 非痛璧性 심근경색 후 좌심실 재성형 및 Transforming Grawth Factor β-1의 발현 변화와 이에 대한 레닌 안지오텐신계 차단제의 효과 분석 Effects on Transforming Growth Factor - β-1 Expression

연태진,김석연,김효수,김어진,김소영,정은주,서정욱,오병희 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.9

본태성 고혈압 환자에 있어서 Losartan(Cozaar^ⓡ)의 효과에 관한 임상적 관찰

양태현,이일,최경환,전희득,송진호,류종철,김두일,김동수 인제대학교 1999 仁濟醫學 Vol.20 No.1

레닌-안지오텐신 계를 차단하는 약물로서 현재 임상적으로 널리 사용하고 있는 유효한 약물은 ACE 억제제이다. 경구 투여로써 유효한 ACE 억제제는 본태성 고혈압, 신혈관성 고혈압 및 심부전증의 치료에 매우 유용하게 사용되고 있다. 그러나 ACE 억제제는 안지오텐신-I에서 안지오텐신-II로 변환을 억제할 뿐 아니라, 강력한 염증 매개체인 bradykinin의 대사를 억제하여 마른 기침이나 혈관 부종 등의 부작용이 발현되어 그 사용에 제한이 있다. 최근 안지오텐신 수용체의 하나인 AT1수용체를 차단할 수 있는 경구용 약제인 안지오텐신-II 수용체 길항제가 개발되어 강압제로 임상에 이용되기 시작하였는데, 이것은 레닌-안지오텐신 계를 효과적으로 억제하여 기침, 혈관부종 등의 약물 부작용 없이 효과적인 강압효과를 나타낸다. 본 연구는 1-3기 본태성 고혈압 환자에게 안지오텐신-II 수용체 길항제인 Losartan을 12주간 투여한 후의 강압효과와 내약성 및 안전성을 평가하고자 하였다. Objective: The renin-angiotensin-aldosterone system plays an important role in the pathophysiology of hypertension and has represented an attractive target for drug intervention in the treatment of high blood pressure. Until recently, angiotensin -converting enzyme inhibitors(ACEIs) were the only clinical relevant means for interrupting this system and have been among the most commonly prescribed drugs for hypertension. Angiotensin-II receptor antagonists(AIIRA) are selective blockers of the renin-angiotensin-aldosterone system and represent an alternative to ACEIs in the treatment of hypertension. Losartan potassium, an orally active, highly selective nonpeptide ATI angiotensin II receptor antagonist, effectively reduces blood pressure by directly blocking receptors. The purpose of this study is to assess the antihypertensive efficacy, safety, and tolerability of losartan in 24 patients with mild to moderate essential hypertension. Methods and Materials: After the wash-out periods of two weeks duration, 50mg losartan once per day was administrated orally for 12 weeks to 24 hypertensive patients. The dose of losartan was increased to 100mg if the mean sitting diastolic blood pressure exceeded 90 mmHg after a 6 week treatment period. Results: After 12 weeks of losartan therapy, mean reductions in sitting systolic, diastolic and mean blood pressure were 21.2mmHg(95% confidence interval 17.5-24), 15.8mmHg(95% confidence interval 13.2-18.3) and 17.3mmHg(95% confidence interval 14.7-19.3), respectively. There were statistically significant differences in the mean reduction of sitting systolic, diastolic and mean blood pressure between baseline and 12th week. Losartan was well tolerated without the adverse reactions. There were no clinically significant laboratory changes before and after the losartan therapy. Conclusion: These results demonstrate that losartan given once a day was effective and safe antihypertensive agent in the treatment of mild to moderate essential hypertension.

ABCB1 c.2677G>T/c.3435C>T diplotype increases the early‑phase oral absorption of losartan

Hyo‑Bin Shin,Eui Hyun Jung,Pureum Kang,Chang Woo Lim,Kyung‑Yul Oh,Chang‑Keun Cho,Yun Jeong Lee,Chang‑Ik Choi,Choon‑Gon Jang,Seok‑Yong Lee,Jung‑Woo Bae 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.11

Losartan has been shown to be a substrate of thedrug-efflux transporter MDR1, encoded by the ABCB1 gene. ABCB1 c.2677G>T and c.3435C>T variants are knownto be associated with reduced expression and function ofP-glycoprotein (P-gp). We investigated the effects of ABCB1diplotype on the pharmacokinetics of losartan. Thirty-eighthealthy Korean volunteers with different ABCB1 diplotypes[c.2677G> T and c.3435C>T; carriers of GG/CC(n = 13), GT/CT (n = 12) and TT/TT (n = 13) diplotype]were recruited and administered a single 50 mg oral doseof losartan potassium. Losartan and its active metaboliteE-3174 samples in plasma and urine were collected up to10 and 8 h after drug administration, respectively, and theconcentrations of both samples were determined by HPLCmethod. Significant differences were observed in Cmax oflosartan and losartan plus E-3174 (Lo + E) among the threediplotype groups (both P < 0.01). However, the power ofthe performed test is less than the desired power (0.800). The tmax of losartan and E-3174 in three diplotype groups were also significantly different (both P < 0.01). The AUCvalues of Lo + E were significantly different among thethree diplotype groups until 6 h after losartan administration(P < 0.01). On the contrary, AUC at the periods of 8–10 hand 10 h-infinity of Lo + E were significantly lower in theTT/TT group than in the GG/CC group. Urinary excretionof losartan until 4 h after losartan administration in the TT/TT group was higher than that of the GG/CC group. Theseresults suggest that c.2677G>T/c.3435C>T diplotypes ofABCB1 may significantly increase the early-phase absorptionof losartan, but not the total absorption.

만성 사구체 신염 환자에서 안지오텐신 수용체 차단제 투여가 요중 TGF-β1에 미치는 효과

박형천 ( Park Hyeong Cheon ),김범석 ( Kim Beom Seog ),최훈영 ( Choe Hun Yeong ),강신욱 ( Kang Sin Ug ),최규헌 ( Choe Gyu Heon ),하성규 ( Ha Seong Gyu ),이호영 ( Lee Ho Yeong ),한대석 ( Han Dae Seog ) 대한신장학회 2004 Kidney Research and Clinical Practice Vol.23 No.2

배 경 : 사구체 신질환애서 TGF-β1의 증가는 세포외기질의 축적을 증가시켜 사구체경화증과 간질의 섬유화를 유발하며 다양한 신질환의 진행을 촉진시킨다. 본 연구에서는 단백뇨가 동반된 비당뇨병성 만성 사구체 신염 환자에서 6개월간의 지속적인 안지오텐신 수용체 차단제 치료에 따른 단백뇨와 TGF-β1 분비 억제 효과 및 요중 T`GF-β1의 임상적 의의를 관찰하고자 하였다. 방 법 : 일일 단백뇨가 1 gm 이상 동반된 비당뇨병성 만성 사구체 신염 활자들을 대상으로losartan 50 ㎎과 100 ㎎을 각각 순차적으로 12주씩 투약하였다. 두 치료 기간 전후로 환자군의 임상적 지표와 혈청 및 요중 TGF-β1 농도를 측정하였고, losartan 투여 24주 후의 요단백 배설 감소 정도에 따라 반응군 (기저 단백뇨에 비해 24주 후 30% 이상 단백뇨가 감소)과 비반응군 (기저 단백뇨에 비해 30% 미만 감소)으로 분류하여 양군의 임상적 특성을 비교하고, 요중 TGF-β1을 포함한 임상적 지표와 losartan에 대한 요단백 감소 반응과의 연관성을 검정하였다. 결 과 : 충 42명의 환자가 치료를 완료하였고, 환자관 모두 치료 전후 혈액생화학적 지표 및 크레아티닌 청소율의 유의한 변화는 없었다. 연구 기간 중 환자군의 혈압이 대부분 목표 혈압 이하로 조절되었으며 요단백 배설 감소 정도에 따른 반응군 (n=31)과 비반응군 (n=11)의 혈압 하강 정도는 비슷하였다. 환자군의 치료 전 요중 TGF-β1 농도는 정상 대조군에 비해 유의하게 높았고, 혈청 TGF-β1 농도는 정상 대조군과 차이가 없었다. 반응군에서 50 ㎎과 100 ㎎의 losartan 치료는 단백뇨 (46%와 64.1%)와 요중 TGF-β1 분비 (29.0%와 45.8%)를 각각 감소시켰으나 (p<0.05), 비반응군에서는 요중 TGF-β1 분비가 초기 12주만 감소 효과가 관찰되었다. 한편 혈청 TGF-β1 농도는 losartan 치료 전후에 유의한 변화가 관찰되지 않았다. 요중 TGF-β1 농도와 단백뇨 배설 정도 및 크레아티닌 청소율 사이에는 유의한 상관관계가 없었다. 그러나 losartan 치료에 따른 요중 TGF-β1 분비 감소 비율과 단백뇨 감소 비율간에 밀접한 양의 상관관계가 관찰되었다 (r=0.301, p=0.052). 비반응군은 반응군에 비해 고령이었고, 기저 요단백 배설 정도와 요중 TGF-β1 농도가 유의하게 높았으며, losartan 치료에 빠른 요중 TGF-β1 분비 감소 비율이 현저히 작았다. 반응군과 비반응군의 로지스틱 분석 상 기저 요중 TCF-β1 농도가 낮을수록 losartan 치료에 따른 단백뇨 감소 반응이 좋았다. 결 론 : 단백뇨가 동반된 비당뇨병성 만성 사구체 신염 환자에서 요중 TCF-β1 농도는 losartan 치료에 따라 유의하게 감소하였고, 단백뇨 감소 반응군과 비반응군 사이의 임상지표 분석상 기저 요중 TGF-β1 농포는 안지오텐신 수용체 차단제 치료에 따른 요단백 감소 반응을 예견할 수 있는 지표임이 관찰되었다. Background : Urinary TGF-β1 reflects intrarenal TGF-β1 production and is increased in patients with progressive nephropathies. We studied the effects of angiotensin receptor blocker (ARB) on serum and urinary TGF-β1 excretion in chronic glomerulonephritis patients with proteinuria. Also the role of urinary TGF-β1 in ARB induced antiproteinuric responses was evaluated. Methods : Patients with non-diabetic chronic renal disease with proteinuria of 1 g or more were enrolled in this open, prospective study. After four weeks of washout period, the patients received losartan 50 mg daily followed by 100 mg in two treatment periods each lasting 12 weeks. Clinical parameters and urinary indices including proteinuria and urinary TGF-β1 were measured at baseline and after each 12 week treatment period. Results : Among the 42 patients who completed the study, 31 responded to ARB therapy determined as a decrease in proteinuria by 30% (responders), and 11 did not respond (non-responders), ARB treatment controlled blood pressure to a similar degree in both responders and non-responders. Renal function and other biochemical parameters did not change during the study period. Both doses of losartan significantly lowered proteinuria and urinary TGF-β1 excretion in responders (50 mg : 33.4% and 29.0%, 100 mg : 64.1% and 45.8%, respectively, p<0.05). In contrast, non-responders showed no significant reduction in proteinuria and no further decrease in urinary TGF-β1 after 100 mg treatment. Urinary TGF-β1 excretion lacked any correlation between clinical parameters such as proteinuria or renal function. Responders were younger, showed lower baseline proteinuria and urinary TGF-β1 excretion and greater reduction in urinary TGF-β1 excretion after ARB treatment. However, lower baseline urinary TGF-β1 excretion was the only significant predictor of response to ARB therapy. Conclusion : Our data suggest that ARB therapy in nondiabetic proteinuric chronic glomerulonephritis patients reduces proteinuria and urinary TGF-β1 excretion and baseline urinary TGF-β1 excretion may predict antiproteinuric response to ARB therapy. (Korean J Nephrol 2004;23(2):231-240)

선천성 고혈압흰쥐 적출대동맥에서 Nitric Oxide와 관련된 이완 반응에 Losartan이 미치는 영향

박봉기(Bong-Gee Park),한형수(Hyung-Soo Han),김중영(Choong-Young Kim) 대한약리학회 1994 대한약리학잡지 Vol.30 No.3

선천성고혈압흰쥐 (SHR)에서 angiotensin converting enzyme inhibitor (ACEI)를 처치하면 내피세포 의존적 이완이 증진된다고 알려져 있다. 본 실험은 angiotensin II가 nitric oxide (NO)와 관련되어 일어나는 적출 대동맥의 이완력에 변화를 주는지 관찰하고자 angiotensin II 작용 억제를 위해 angiotensin II 수용체 차단제인 losartan과 ACEI인 enalapril을 사용하였으며 혈관에서의 NO는 혈관내피세포에서 생성되는 constitutive NO와 주로 혈관 평활근에서 LPS에 생성되는 inducible NO가 있으므로 이들 양자에 대한 angiotensin II의 작용을 검토하였다. 2주간 losartan (30 mg/kg/day)과 enalapril (10 mg/kg/day)을 처치한 경우 acetylcholine (10^-9 to 10^-5 M)과 histamine (10^-8 to 10^-4 M)에 의한 이완 반응이 증가되었으나 90분간 적출 대동맥에 losartan (10^-4 M) 을 노출시킨 경우는 이완 반응에 변화가 없었다. Phenylephrine (10^-7 M) 을 2시간 간격으로 반복 투여하여 수축시킨 경우 LPS (100μg/ml)처치에 의해 시간이 지남에 따라 수축력이 감소되었고 대조군에서는 수축력이 감소되지 않았다. LPS 처치에 따른 phenylephrine에 의한 수축력의 감소는 enalapril이나 losartan을 2주간 처치한 경우에도 영향을 받지 않았다. 이상의 결과로 미루어 아마도 losartan의 내피세포에 대한 작용은 constitutive NO 생성을 증가시키나 inducible NO 생성에는 영향을 미치지 않을 것으로 여겨진다. It is well known that angiotensin converting enzyme inhibitors(ACEIs) increase endothelium-dependent relaxation in aortic strips of spontaneously hypertensive rats(SHR) and this increase in relaxation may be due to altered endothelial nitric oxide breakdown. But there are few studies on the effect of the angiotensin II receptor blocker on the nitric oxide-mediated relaxation. So we attempted to investigate the effect of angiotensin II receptor blocker on the nitric oxide-dependent relaxation in isolated aorta of SHR. Two week-treatment of losartan (30 mg/kg/day) increased the acetylcholine(10^-9 to 10^-5 M)-and histamine(10^-8 to 10^-4 M)-induced relaxation in endothelium intact strips but 90 minutes-treatment of losartan (10^-4 M) showed no increase in relaxation. The phenylephrine (10^-7 M)-induced contraction, repeated every 2 hours, was diminished gradually following lipopolysaccharide (LPS)-treatment (100μg/ml) but there was no significant difference in enalapril- and losartan-treated group compared with control group. These results suggest that activity of the endothelial constitutive NO synthase may be changed by chronic treatment of angiotensin II receptor blockers and ACEIs but angiotensin II antagonist and ACEI have no effect on the inducible NO synthase activity in the isolated aorta of SHR

고혈압 환자에서 Losartan(Cozaar^(�))의 임상적 효과

김남호,정명호,박우석,김성희,김준우,조장현,안영근,김남호,박주형,조정관,박종춘,강정채 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.8