• 생명과학회지
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• 제20권7호
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• pp.969-976
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• 2010

피리딜 이미다졸 시리즈의 비펩타이드 안지오텐신 수용체 리간드로 새롭게 개발된 KR-31125에 대한 생체 내활성을 동물모델에서 검증하였다. 척수장애 동물모델에서 KR-31125는 비대칭 농도의존적으로 로자탄보다 18배 이상의 경쟁적인 혈압강하 효과를 나타내었으며, 기타 수용체 촉진제들의 영향을 받지 않았다. 안지오텐신으로 유도된 정상혈압 쥐모델에서는 대조화합물인 로자탄과 비교하여 경구효과는 동등하였으나 더 빠른 초기효과가 관찰되었다. 또한 신성고혈압 쥐모델에서 KR-31125는 로자탄보다 3배 이상의 지속형 혈압강하 효과를 나타내었고, 이뇨제를 투여하여 레닌을 활성화시킨 개실험 모델에서 KR-31125는 로자탄보다 20배 이상의 지속적인 경구혈압강하 효과를 나타내었다. 이러한 KR-31125의 생체 내 활성특징은 대사물질을 통하여 효과를 발휘하는 로자탄과 달리 동일물질의 효과에 의한 것으로 고혈압 및 혈관질환과 깊은 관련이 있는 안지오텐신 조절시스템에 대한 세포영상, 비침투성 진단등의 도구물질로서 가능성이 높을 것으로 판단된다.

• Biomolecules & Therapeutics
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• 제8권1호
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• pp.93-98
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• 2000

This study has been carried out to investigate general pharmacological action of bamboo salt (jukyom) in terms of effects on central nervous system and cardiovascular system in experimental animals. After bamboo salt, crude salt or reagent-grade NaCl were orally administered into male ICR mice with dose of 2.0 g/kg, general behavioural syndromes such as body weight and locomotor activity, spontaneous motor activity, pento-barbital-induced sleeping time, muscle incoordination, electroshock-induced convulsion, body temperature and writhing response caused by 0.6% acetic acid solution were observed. Bamboo salt had no influences in these indices for examinition of effect on central nervous system. Additionally, conscious male Sprague Dawley rats fastened overnight won ere treated with bamboo salt, crude salt or reagent-grade NaCl (2.0 g/kg, p.o.) to examine the effect of these salts cardiovascular system. Systolic, median and diastolic food pressure and heart rate were dertemined using tail cuff indirect method. Treatment with Hydralazine (50 mg/kg, p.o) as a positive control produced the decreases in systolic, median and diastolic blood treasure and an increase in heart rate. whereas no changes were observed in bamboo salt, crude salt and reagent-grade NaCl treated groups. These results strongly suggest that bamboo salt may have no effects on general pharmacology of central nervous systems and cardio-vascular systems.

• Biomolecules & Therapeutics
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• 제5권4호
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• pp.390-401
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• 1997

In order to investigate the pharmacological properties of New Woohwangchungsimwon Liquid (NCL), effects of Woohwangchungsimwon Liquid (CL) and NCL were compared. In isolated rat aorta, NCL and CL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) without regard to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxation of NCL and CL. NCL and CL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NCL and CL significantly decreased heart rate. NCL and CL, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NCL and CL had no effects on parameters of action potential at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NCL and CL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between two preparations.

• Biomolecules & Therapeutics
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• 제7권1호
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• pp.66-78
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• 1999

In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD$_{90}$ and V$_{max}$ at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.s.

• 약학회지
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• 제41권6호
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• pp.802-816
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• 1997

In order to investigate the pharmacological properties of New Woohwangehungsimwon Pill (NWCH). Effects of Woohwangehungsimwon Pill (WCH) and NWCH were compared using various experimental models. In isolated rat aorta, NWCH and WCH showed the relaxation of blood vessels in maximum contractile response to phenylephrine ($10^{-6}$M) without regard to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxative effects of NWCH and WCH. NWCH and WCH inhibited the vascular contractions induced by acethylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats(SHRs), NWCH and WCH decreased significantly heart rate. These, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, these had no effects on parameters of action potential at low doses, whereas inhibited the cardiac, contractility at high doses. Furthermore, these had a significant inhibitory effects on heart acceleration in normotensive rats and SHRs. These results suggested that NWCH and WCH have weak cardiovascular effects, and that there is no significant differences between two preparations.

• The Korean Journal of Physiology
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• 제24권2호
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• pp.319-329
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• 1990

장기적으로 소금 섭취량을 달리 한 정상 및 고혈압쥐에서 atrial natriurectic peptide (ANP) 가 혈압, renin-aldosterone 및 신배설에 미치는 효과를 비교하였다. 생후 6주된 spontaneously hyper-tensive rate (SHR)와 Wistar 숫쥐를 각각 저염, 정상염 및 고염 (2, 10, 25 mmol NaCl/100g diet) 군으로 나누어 실험 식이를 6주동안 먹었다. 실험 당일 아침에 쥐를 ether로 마취시킨 상태에서 대퇴 동맥과 정맥 및 방광에 catheter를 삽입한 다음에 쥐를 restraining cage에 넣어 고정시켰다. 마취가 깨고 혈압이 안정된 후에 정맥관으로 0.9% saline을 0.02ml/min의 속도로 80분간 주입하고 안정시 뇨와 혈액을 채취하였다. 그후 ANP를 380 ng/kg/min의 속도로 20분간 주입하였으며 그동안 10분 간격으로 요를 채취한 다음 채혈하였다. 혈장 aldosterone 농도와 renin 활성도 (PRA)를 방사면역법으로 측정하였다. ANP를 주입하기 전에 SHR 고염군의 평균동맥압은 정사염이나 저염군보다 유의하게 높았으나, Wistar의 혈압은 소금군 사이에서 차이가 없었다. ANP 주입전의 혈장 aldosterone 농도는 소금 섭취량이 많을수록 유의하게 낮았으며, Wistal 군이 SHR 보다 높은 값을 보였다. 혈장 renin 활성도는 소금군 간에 차이가 없었으며, Wistar와 SHR 간에도 차이가 없었다. 요량이나 Na, K 배설률은 소금군 간에 유의한 차이가 없었으나, SHR이 Wistar 보다 높은 경향을 보였다. Hematocrit 값도 소금군 간에 차이가 없었으나, SHR의 값이 Wistar 보다 유의하게 높았다. ANP를 주입하는 동안 혈압이 점진적으로 감소하여 20분후에는 $20{\sim}30\;mmHg$ 정도 감소하였으나, 각 소금군사이에 차이가 없었다. 그러나, ANP에 의한 혈압 강하 정도는 SHR이 Wistar 보다 유의하게 높았다. ANP 주입 후에는 모든 군에서 aldosterone과 혈장 renin 활성도가 유의하게 감소하였는데, aldosterone의 감소 정도는 저염군에서 가장 크게 나타났다. ANP의 이뇨 및 Na 배설 항진효과는 Wistar에서는 소금군 간에 차이가 없었으나, SHR 에서는 고염군의 Na 배설률이 저염군보다 유의하게 높았다. ANP의 혈압강하 효과나 Na 배설 항진효과가 SHR에서 Wistar 보다 유의하게 높게 나타났으나, 이뇨반응, renin 및 hematocrit의 변화에는 차이가 없었다. 이상의 결과에서, 장기적으로 소금 섭취량이 다름에 따라 ANP의 효과 중에서 특히 aldosterone 분비나 SHR의 Na 배설에 차이가 나타났는데 그 작용 기전은 확실치 않다.