<i>In vitro</i> and <i>in vivo</i> evaluation of a novel polymer-free everolimus-eluting stent by nitrogen-doped titanium dioxide film deposition

Park, Dae Sung,Bae, In-Ho,Jeong, Myung Ho,Lim, Kyung Seob,Sim, Doo Sun,Hong, Young Joon,Lee, So-Youn,Jang, Eun Jae,Shim, Jae-Won,Park, Jun-Kyu,Lim, Han Chul,Kim, Han Byul Elsevier 2018 Materials Science and Engineering C Vol.91 No.-

<P><B>Abstract</B></P> <P>Inflammation and thrombosis are linked to the use of polymer-based drug-eluting stents (DES). The aim of this study was to develop a polymer-free everolimus (EVL)-eluting stent using nitrogen-doped titanium dioxide (N-TiO<SUB>2</SUB>) and verify its efficacy by <I>in vitro</I> and <I>in vivo</I> assessment in a porcine coronary model. Various analytical approaches such as scanning electron microscopy and atomic force microscopy, electron spectroscopy, Fourier transform infrared spectrometry and contact angle measurement were employed for the characterization. As a part of biocompatibility assessment, platelet adhesion and smooth muscle cell (SMC) proliferation were examined. Bare metal stent (BMS), N-TiO<SUB>2</SUB> stent, everolimus-eluting N-TiO<SUB>2</SUB> (N-TiO<SUB>2</SUB>-EVL) stent, and commercialized EVL-eluting stent (EES) were randomly placed in forty coronary arteries in twenty pigs. After four weeks of implantation, the stents were subjected to histological and quantitative analysis. The N-TiO<SUB>2</SUB> film used in this study was well coated without any cracks or peeling. Surface hydrophilicity (88.8% of angle decrement) could be associated with the decrease in surface roughness post N-TiO<SUB>2</SUB> deposition (37.0%). The platelet adhesion on the N-TiO<SUB>2</SUB> surfaces was less than that on the BMS surface. The proliferation of SMC was suppressed in the N-TiO<SUB>2</SUB>-EVL group (30.2%) but not in the BMS group. In the animal study, the percent area restenosis was significantly decreased in the N-TiO<SUB>2</SUB>-EVL group compared to that in the BMS group. The results (BMS; 47.0 ± 11.00%, N-TiO<SUB>2</SUB>-EVL; 31.7 ± 10.50%, and EES; 29.1 ± 11.21%, <I>n</I> = 10, <I>p</I> < 0.05) were almost at par with those of the commercialized EVL-eluting stent. The introduction of N-TiO<SUB>2</SUB> deposition during fabrication of polymer-free DES may be an efficient accessorial process for preventing in-stent restenosis and thrombosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> N-TiO<SUB>2</SUB> surfaces can help to reduce the platelet adhesion. </LI> <LI> In porcine model, N-TiO<SUB>2</SUB> everolimus decreased in-stent restenosis and fibrin deposition. </LI> </UL> </P>

In-direct localized surface plasmon resonance (LSPR)-based nanosensors for highly sensitive and rapid detection of cortisol

Jeon, Jinwoo,Uthaman, Saji,Lee, Jiyoung,Hwang, Hyejin,Kim, Gibum,Yoo, Pil J.,Hammock, Bruce D.,Kim, Christine S.,Park, Yeon-Su,Park, In-Kyu Elsevier 2018 Sensors and actuators. B, Chemical Vol.266 No.-

<P><B>Abstract</B></P> <P>Over-secretion of cortisol from the adrenal cortex is closely related to acute and chronic stress; thus, rapid and sensitive detection of cortisol in serum is of critical importance for preventing the progression of stress-related diseases. The binding of a biological molecule to the surface of metallic nanoparticles changes the local refractive index and in turn induces a shift in the localized surface plasmon resonance (LSPR) wavelength. Utilizing this phenomenon, we designed a novel disposable LSPR-based cuvette-type sensor for detecting cortisol in serum. The developed cuvette-type nanosensor consists primarily of an assembly of plastic unit sensors coated with gold nanoparticles on a single layer wherein cortisol-conjugated bovine serum albumin (BSA) is immobilized. In this system, a redshift in LSPR wavelength is induced by the binding of cortisol antibody onto cortisol-conjugated BSA immobilized on a gold nanoparticle surface in the nanosensor. In a competitive assay, the nanosensor could rapidly detect cortisol in both a PBS solution and serum (within 20 min) at concentrations ranging from 1 to 10,000 ng/mL (2.759–3 × 10<SUP>3</SUP> nmol/L), which is comparable to conventional enzyme-linked immunosorbent assay (ELISA) which typically requires longer than 4 h and complex sample preparation. Thus, we demonstrated that the LSPR-based nanosensor system developed in this study can provide a useful toolkit for a rapid, highly sensitive and reliable detection of cortisol hormone in a commercially available manner.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Novel disposable LSPR-based cuvette-type sensor for detecting cortisol in serum. </LI> <LI> Rapid, convenient, and sensitive method for detecting cortisol hormone in serum. </LI> <LI> Detect cortisol in both PBS solution and serum within 20 min at concentrations ranging from 1 to 10,000 ng/mL. </LI> </UL> </P>

Uncoupling Protein 3의 골격근 세포내 과발현이 OLETF 백서 및 배양된 골격근 세포에서 포도당대사에 미치는 영향

한정희,박혜선,고정민,김하영,강호경,이인규,박중열,홍성관,이재담,이기업 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.25 No.6

연구배경:Uncoupling protein(UCP)는 미토콘드리아의 내막에 위치하는 단백질로 세포내의 과다한 에너지를 열로 발산시키는 기능을 가진다. 최근 동물의 갈색지방조직에만 존재하는 UCP와 유사성을 가진 아형들(UCP2,3)이 사람에게도 존재함이 알려져 큰 관심을 끌도 있는데 이중 UCP3는 그 발현이 골격근세포와 갈색지방조직에만 국한된다. 본 연구에서는 UCP3가 체내 인슐린 감수성을 결정하는데 가장 중요한 조직인 골격근에 국한되어 발현되는 점에 착안하여 UCP3를 골격근세포에 과발현시켰을 때 포도당 대사에 어떠한 영향이 나타나는 지를 조사하였다. 방법:25주령의 8마리의 OLETF 백서를 대상으로 하여 4마리는 골격근에 adenovirus 2mL(1×10¹²pfu/mL)를 주사하여 대조군으로 하였고 4마리는 골격근에 재조합법으로 제작된 adenovirus­UCP3 2mL(1×10¹²pfu/mL)를 주사하였다(UCP3 과발현군). UCP3를 투여한 백서에서 먹이섭취가 증가하는 경향이 있어 그 전날 대조군이 먹은 야의 먹이만큼 투여하였다. 골격근에 adenovirus를 주사한 10일 후에 euglycemic hyperinsulinemic clamp를 시행하였다. Adenovirus­UCP를 C2C12 골격근 세포에 transfection시켜 UCP3를 C2C12 골격근 세포에 transfection시켜 UPS3­C2C12를 만들고 C2C12 골격근 세포와 UPS3­C2C12 골격근 세포에서 포도당 수송 및 당원합성을 측정하였다. 결과:UCP3 과발현 OLETF에서 체중이 감소하는 경향을 보였고 인슐린 감수성이 증가하였다. C2C12세포에서 기저상태 포도당 수송은 1.28±0.17μmol/L/min였고 100nM 인슐린으로 2시간 처리한 후 2.67±0.20 μmol/L/min로 증가하였다. UCP3­C2C12 세포에서는 기저상태 포도당 수송이 3.98±0.13μmol/L/min로 증가되었고 인슐린 처리 후 5.74±0.44μmol/L/min로 증가하였다. 인슐린을 처리한 UCP3­C2C12 세포에 P13K 억제제인 wortmannin을 첨가하였을 때 포도당 수송활성이 3.81±0.20μmol/L/min로 감소하였다. 기저상태 당원합성은 C2C12 세포에서 0.25±0.01μmol/L/min였고 인슐린 처리 후 0.45±0.01μmol/L/min로 증가하였다. UCP3­C2C12 세포에서는 기저상태 당원합성이 0.62±0.01μmol/L/min였고 인슐린 처리 후 1.26±454μmol/L/min로 증가하였다. UCP3­C2C12세포에 wortmannin을 첨가하였을 때 당원합성율이 0.80±0.04μmol/L/min로 감소하였다. 결론:UCP3 과발현이 OLETF 백서에서 인슐린 감수성을 증가시켰고 골격근세포에서 포도당 수송 및 당원합성을 증가시켰다. wortmannin을 첨가하였을 때 포도당 수송 및 당원합성이 감소함으로 보아 이 과정이 인슐린 신호전달체계인 P13K에 일부 의존함을 알 수 있었다. Background : UC P3 is a mitochondrial membrane protein expressed selectively in the skeletal muscle and brown adipose tissue. Since the skeletal muscle is the main organ determining insulin sensitivity in the body, it was hypothesized that UCP3 overexpression in skeletal muscle cells would improve glucose metabolism. Methods : An adenovirus-UCP3 was produced by a recombinant DNA method. OLETF rats were divided into 2 groups. Four rats were injected with the adenovirus-UCP3 (UCP3 group) and others were injected with the adenovirus(control group) in the skeletal muscle. The UCP3 group was provided with the same quantity of food as that consumed by the control group on the previous day. Insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp method. In a separate experiment, glucose transport and glycogen synthesis we evaluated in C2C212 cells transfected with ether an adenovirus or the adenovirus-UCP3. Results : The insulin sensitivity improved significantly and the body weight decreased in the UCP3 group. The glucose transport and glycogen synthesis were higher in the UCP3-C2C12 skeletal muscle cells at the basal state. After insulin treatment, glucose transport and glycogen synthesis were also higher in the UCP3-C2C12 cells but the increments were reduced after treatment with wortmannin, a PI3K inhibitor. Conclusion : Insulin sensitivity was higher in the UCP3-overexpressed OLETF rats in the in vivo study. UCP3 transfection also increased glucose transport and glycogen synthesis in the cultured skeletal muscle cells by a PI3K dependent mechanism(J Kor Diabetes Asso 25 :460~468, 2001).

Nelumbinis Semen Reverses a Decrease in $5-HT_{1A}$Receptor Binding Induced by Chronic Mild Stress, a Depression-like Symptom

Jang, Choon-Gon,Kang, Moon-Kyu,Cho, Jae-Han,Lee, Sun-Bok,Kim, Hyun-Taek,Park, Soon-Kwon,Lee, Jin-Woo,Park, Seong-Kyu,Hong, Moo-Chang,Shin, Min-Kyu,Shim, In-Sup,Bae , Hyun-Su The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.10

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of $5-HT_{1A}$ receptors. The present study assessed if Nelumbinis Semen (N. s.) had an anti-depression effect through reversing a decrease in $5-HT_{1A}$receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a $5-HT_{1A}$ receptor binding assay, with a specific $5-HT_{1A}$receptor agonist, 8- OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N. s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N. s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H. p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N. s. The N. s. treatment significantly reversed the decreased sucrose intake under CMS (P<0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N. s. and H. p. reversed the CMS-induced decrease in $5-HT_{1A}$receptor binding. In the I to II regions of the frontal cortex, N. s. and H. p. also reversed the CMS-induced decrease in$5-HT_{1A}$receptor binding, and even showed a significant increase in $5-HT_{1A}$receptor binding compared to the F treatment group (N. s. vs. P, p<0.05, H. p. vs. P, p<0.05). However, in the hypothalamus, all treatments reversed the CMSinduced decrease in $5-HT_{1A}$receptor binding. This reversal effect of N. s. on the decrease in $5-HT_{1A}$receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H. p, but different from that of F. It is concluded that N. s. presents an anti-depression effect through enhancing $5-HT_{1A}$receptor binding.

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.

I-Muscone의 심혈관계에 관한 약리연구

조태순,김낙두,허인회,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 l-muscone, effects of l-muscone and musk were studied on the cardiovascular system with various experimental models. In isolated rat aorta, l-muscone and musk made the relaxation of blood vessels in maximum contractile response to phenylephrin (10^-6M) in endothelium-containing rings of the rat aorta, but not in endothelium-denuded rings. However, l-muscone and musk in the presence of the inhibitor of NO synthase and guanylate cyclase did not make the relaxation of blood vessel. In spontaneously hypertensive rats (SHRs), l-muscone and musk slightly reduced blood pressure but significantly decreased heart rate. In the isolated perfused rat hearts. l-muscone and musk did not affect significantly on LVDP, contractile force, coronary flow and (-dp/dt)/(+dp/dt). These results suggest that l-muscone and musk have weak cardiovascular effects with relaxation of blood vessel and decrease of heart rate, but without significant cardiac functions.

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.

Glucotoxicity in the INS-1 Rat Insulinoma Cell Line Is Mediated by the Orphan Nuclear Receptor Small Heterodimer Partner

Park, Keun-Gyu,Lee, Kyeong-Min,Seo, Hye-Young,Suh, Ji-Ho,Kim, Hye-Soon,Wang, Li,Won, Kyu-Chang,Lee, Hyoung-Woo,Park, Joong-Yeol,Lee, Ki-Up,Kim, Jung-Guk,Kim, Bo-Wan,Choi, Hueng-Sik,Lee, In-Kyu American Diabetes Association 2007 Diabetes Vol.56 No.2

<P>Prolonged elevations of glucose concentration have deleterious effects on beta-cell function. One of the hallmarks of such glucotoxicity is a reduction in insulin gene expression, resulting from decreased insulin promoter activity. Small heterodimer partner (SHP; NR0B2) is an atypical orphan nuclear receptor that inhibits nuclear receptor signaling in diverse metabolic pathways. In this study, we found that sustained culture of INS-1 cells at high glucose concentrations leads to an increase in SHP mRNA expression, followed by a decrease in insulin gene expression. Inhibition of endogenous SHP gene expression by small interfering RNA partially restored high-glucose-induced suppression of the insulin gene. Adenovirus-mediated overexpression of SHP in INS-1 cells impaired glucose-stimulated insulin secretion as well as insulin gene expression. SHP downregulates insulin gene expression via two mechanisms: by downregulating PDX-1 and MafA gene expression and by inhibiting p300-mediated pancreatic duodenal homeobox factor 1-and BETA2-dependent transcriptional activity from the insulin promoter. Finally, the pancreatic islets of diabetic OLETF rats express SHP mRNA at higher levels than the islets from LETO rats. These results collectively suggest that SHP plays an important role in the development of beta-cell dysfunction induced by glucotoxicity.</P>

PC12 세포에서 Sertraline을 위시한 항우울제에 의한 칼슘길항 유사효과

박기창,공인덕,정해숙,한준규,박규상,이중우,백인호 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.3

본 실험에서는 PC12 세포를 신경세포 모델로 형광물질인 fura-2 및 bisoxonol을 이용하여 세포내 유리 칼슘이온 농도 및 막전압을 각각 측정하여 화학구조가 서로 다른 몇몇 항우울제가 막전압 의존성 칼슘통로의 활성화 및 ATP를 통한 수용체 의존성 칼슘통로의 활성화에 미치는 영향을 관찰하여 아래와 같은 결과를 얻었다. 1) 선택적 serotonin 재흡수 억제제의 하나인 sertraline은 60mM KCI 자극 및 100μM ATP 자극에 의한 [Ca²+]i의 증가를 억제하였으며 이때 IC50 값은 각각 2.5μM과 5.3μM이었다. 2) 막전압 의존성 칼슘통로 및 ATP에 의한 수용체 의존성 칼슘통로의 억제효과는 sertraline을 비롯한 선택적 serotonin 재흡수 억제제나 삼환계 항우울제인 경우 크나, 비전형 항우울제인 trazodone 이나 MAO 억제제인 moclobemide의 경우에는 효과가 미미했다. 3) Sertraline 자체는 농도 의존적으로 지속적인 막전압의 탈분극을 유발하였으며 이에 따라 안정시의 세포내 유리 칼슘이온 농도를 일부 증가시켰다. 4) Sertraline에 의한 칼슘이온 농도 증가효과는 일부 세포내 Ca²+ 저장소로부터 동원이 관여하나 주로 세포막을 통한 칼슘유입에 의해 일어난다. 5) 여러 항우울제 중 sertraline에 의한 탈분극 효과가 가장 컸으며 그 외의 선택적 serotonin 재섭취 억제제, 삼환계 항우울제들은 탈분극 효과가 있었으나 비전형 항우울제인 trazodone은 일부의 효과를 그리로 MAO 억제제인 moclobemide는 막전압에 전혀 영향을 주지 않았다. 6) ATP는 일시적인 탈분극을 유발하였는데 sertraline 전처지로 탈분극 효과가 억제되었으며 이때 IC50는 30μM이었다. 7) ATP에 의한 세포내 칼슘이온 농도의 증가는 nimodipine에 의해 일부만 억제되었으나 sertraline을 함께 투여한 경우에는 그 억제 효과가 훨씬 더 증가하였다. 이상의 실험결과로 미루어 보아 항우울제 중에서 sertraline을 비롯한 선택적 serotonin 재흡수 억제제나 삼환계 항우울제들은 신경세포를 지속적으로 탈분극 시키고 세포내 유리 칼슘농도를 증가시키는 한편 막전압 의존성 칼슘통로와 수용체 의존성 칼슘통로를 차단하여 그 효과가 나타나는 것으로 사료된다. It has been known that antidepressants have calcium antagonist-like action in neuronal tissues. However, their mechanisms are still obscure. For the study of neurochemical mechanism of antidepressants, the authors examined the effects of antidepressants(1-100μM) on the intracellular Ca²+ concentration ([Ca²+]i) and the membrane potential in PC12 cells using fluorescent dyes, fura-2/AM and bisoxonol, respectively. The results were as follows : 1) Sertraline, a selective serotonin reuptake inhibitor(SSRI), inhibited the increment of [Ca²+]i induced by high 60 mM KCl and 100μM ATP with an IC50 value of 2.5μM and 5.4μM, respectively. 2) SSRIs(sertraline, paroxetine and fluoxetine) and tricyclic antidepressants(imipramine and amitriptyline) had strong effects on the inhibition of both voltage-dependent Ca²+ channel and receptor-dependent Ca²+channel, whereas atypical antidepressant(trazodone) and MAO inhibitor(moclobemide) had little effects. 3) Sertraline itself depolarized the membrane potential in a sustained manner depending on its own concentration and it also increased the basal level of [Ca²+]i. 4) The increment of [Ca²+]i might be induced partly by the release from the intracellular calcium store, but mostly induced by the calcium transport through membrane. 5) Among those antidepressants tested, sertraline was the most potent one, Other SSRIs(paroxetine and fluoxetine) and tricyclic antidepressants(imipramine and amitriptyline) were moderately potent. Atypical antidepressant(trazodone) had little effects, and MAO inhibitor(moclobemide) had no effect on the depolarization. 6) External application of ATP induced temporary depolarization. This effect was blocked by prior treatment with sertraline with an IC50 value of 30μM. 7) The increment of [Ca²+]i through voltage-dependent Ca²+ channel was almost inhibited by a selective calcium channel blocker(nimodipine). However, the ATP-induced increment of [Ca²+]i was partially inhibited by nimodipine. These inhibitor effects were potentiated by the addition of sertraline. In the light of these results, it is likely that SSRIs and tricyclic antidepressants could show the blocking effects on both voltage-dependent and receptor-dependent calcium channel by depolarizing neuronal cell membrane potential in a sustained manner and by increasing intracellular free calcium level.

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.