신규 합성 KATP 통로 개방제인 SKP-450과 대사체 SKP-818의 흰쥐 적출 심장 및 대동맥에 대한 작용

정이숙(Yi Sook Jung),문창현(Chang Hyun Moon),유성은(Sung Eun Yoo),신화섭(Hwa Sup Shin) 대한약학회 1997 약학회지 Vol.41 No.2

The effect of potassium channel openers, SKP-450, SKP-818 and lemakalim have been compared in rat heart and aorta. In rat isolated heart, SKP-450 had a greater negative inotropic effect than lemakalim and KR-30818 against left ventricular developed pressure (LVDP) and double product of heart rate and LVDP (DP). In addition, SKP-450 had a greater effect than lemakalim and KR-30818 in increasing coronary flow, indicating a more potent vasodilating effect in coronary artery. Negative inotropic effect and coronary vasodilating effect of SKP-450 and SEP-818 were significantly reduced by 10 min-perfusion with 10-6M glyburide, a selective blocker of ATP-sensitive potassium channel. In rat aorta, SKP-30450 and SKP-30818 as well as lemakalim induced powerful concentration-dependent relaxations against norepinephrinc-induced tone (EC50, mcM : SKP-30450, 0.107 +/- 0.009; SKP-30818, 0.476 +/- 0.022; lemakalim, 0.565 +/- 0.039). These relaxant effects were significantly reduced by pretreatment with glyburide. In sununary, SKP-30450 and SKP-30818 showed greater negative inotropic and vasorelaxant effect than lemakalim in rat aorta with order of potency of SKP-30450 > SKP-30818 > lemakalim. These actions are suggested to be mediated at least in part by a mechanism which involves the opening of ATP-sensitive potassium channel.

신원방우황청심원의 심혈관계에 관한 약효

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,김상호,신대희 대한약학회 1999 약학회지 Vol.43 No.2

In order to investigate the pharmacologic properties of New Wonbang Woohwangchungsimwon Pill(NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10-6 M) regardless 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 relaxing effects of NSCH and SCH. NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCH and SCH decreased significantly heart rate. These, at high doses, had a negative inotropic effects 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 guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA), $V_{max}$ and resting membrane potential (RMP) at low doses, whereas inhibitory the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.

신원방우황청심원액의 심혈관계에 관한 약효

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

Abstract-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.

신원방우황청심원의 심혈관계에 관한 약효

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 성균관대학교 약학연구소 1999 成均藥硏論文集 Vol.11 No.-

Abstract-In order to investigate the phamacological properties of New Wonbang Woohwangchungsimwon Pill (NSCH), effects of Wonbang Woohwangchungsimwon Pill (SCH) and NSCH were compared using various experimental models. In rat aorta, NSCH and SCH made the relaxation of blood vessels in maximum contractile response to phenylephrine (10^-6 M) regardless to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not aftect significantly the relaxing effects of NSCH and SCH, NSCH and SCH inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs). NSCH and SCH decreased significantly heart rate. These, 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 guinea-pig papillary muscle, these had no effects on parameters of action potential such as action potential amplitude (APA). V_max and resting membrane potential (RMP) at low doses, whereas inhibited the cardiac contractility at high doses. Furthermore, these had a significant inhibitory effects on palpitation of the heart in normotensive rats and SHRs. These results suggest that NSCH and SCH have weak cardiovascular effects, and that there is no significant differences between cardiovascular effects of two preparations.

신원방우황청심원액의 심혈관계에 관한 약효

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 충남대학교 약학대학 의약품개발연구소 1999 藥學論文集 Vol.15 No.-

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^-6M) 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.

신우황청심원의 심혈관계에 대한 약효

조태순(Tai Soon Cho),이선미(Sun Mee Lee),허인회(In Hoi Huh),안형수(Hyung Soo Ann),권광일(Kwang Il Kwon),박석기(Seok Ki Park),심상호(Sang Ho Shim),신대희(Dae Hee Shin),박대규(Dai Kyu Park),김낙두(Nak Doo Kim) 대한약학회 1997 약학회지 Vol.41 No.6

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 (10-6M) 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.

신우황청심원액의 심혈관계에 관한 약효연구

조태순,이선미,김낙두,허인회,안형수,권광일,박석기,심상호,신대희,박대규 충남대학교 약학대학 의약품개발연구소 1997 藥學論文集 Vol.13 No.-

In order to investigate the pharmacological properties of New Woohwangchungsimwon Liquid (NCL), efects 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 (10^6M) without regard to intact endothelium or denuded rings of the rat aorta. Furthemore, 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 dosedependent 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 efects 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.