• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.263-270
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• 2000

To evaluate the involvement of nitric oxide production on the endothelium-dependent relaxation in diabetes, we have measured vascular and endothelial function and nitric oxide concentration, and the expression level of endothelial nitric oxide synthase in the streptozotocin-induced diabetic rats. Diabetic rats were induced by the injection of streptozotocin (50 mg/kg i.v.) in the Sprague-Dawley rats. Vasoconstrictor responses to norepinephrine (NE) showed that maximal contraction to norepinephrine $(10^{-5}\;M)$ was significantly enhanced in the aorta of diabetic rats. Endothelium-dependent relaxation induced by acetylcholine was markedly impaired in the aorta of diabetic rats, these responses were little improved by the pretreatment with indomethacin. However, endothelium-independent relaxation induced by nitroprusside was not altered in the diabetic rats. Plasma nitrite and nitrate $(NO_2/_3)$ levels in diabetic rats were significantly lower than in non-diabetic rats. Western blot analysis using a monoclonal antibody against endothelial cell nitric oxide synthase (eNOS) revealed that the protein level was lower in the aorta of diabetic rats than in non-diabetic rats. These data indicate that nitric oxide formation and eNOS expression is reduced in diabetes, and this would, in part, account for the impaired endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats.

• Molecules and Cells
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• 제27권2호
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• pp.191-198
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• 2009

The present study was undertaken to determine whether treatment with genistein, the plant-derived estrogen-like compound influences agonist-induced vascular smooth muscle contraction and, if so, to investigate related mechanisms. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Genistein completely inhibited KCl-, phorbol ester-, phenylephrine-, fluoride- and thromboxane $A_2$-induced contractions. An inactive analogue, daidzein, completely inhibited only fluoride-induced contraction regardless of endothelial function, suggesting some difference between the mechanisms of RhoA/Rho-kinase activators such as fluoride and thromboxane $A_2$. Furthermore, genistein and daidzein each significantly decreased phosphorylation of MYPT1 at Thr855 had been induced by a thromboxane $A_2$ mimetic. Interestingly, iberiotoxin, a blocker of large-conductance calcium-activated potassium channels, did not inhibit the relaxation response to genistein or daidzein in denuded aortic rings precontracted with fluoride. In conclusion, genistein or daidzein elicit similar relaxing responses in fluoride-induced contractions, regardless of tyrosine kinase inhibition or endothelial function, and the relaxation caused by genistein or daidzein was not antagonized by large conductance $K_{Ca}$-channel inhibitors in the denuded muscle. This suggests that the RhoA/Rho-kinase pathway rather than $K^+$- channels are involved in the genistein-induced vasodilation. In addition, based on molecular and physiological results, only one vasoconstrictor fluoride seems to be a full RhoA/Rho-kinase activator; the others are partial activators.

• 동의생리병리학회지
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• 제19권3호
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• pp.743-748
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• 2005

This study was performed for the investigation of vasodilatory efficacy and its underlying mechanisms of Jagumhuan(JGH), a herbal remedy. JGH produced completely endothelium-dependent relaxation and relaxed phenylephrine(PE)-precontracted aorta in a concentration dependent manner. The magnitude of relaxation was greater in PE induced contraction than that of KCl, suggesting involvement of $K^+$ channel in the relaxant effect. Both glibenclamide$(10^{-5}M)$, a $K_{ATP}$ channel inhibitor and indometacin, a cyclooxygenase inhibitor, completely prevented this relaxation. The relaxation effects of JGH, involve in part the release of nitric oxide from the endothelium as pretreatment with L-NAME, an NOS inhibitor, and methylene blue, a cGMP inhibitor, attenuated the responses by 62% and 58%, respectively. In addition, nitrite was produced by JGH in human aortic smooth muscle cells and human umbilical vein endothelial cells. The relaxant effect of JGH was also inhibited by 55.41% by tetraethylammonium(TEA; 5mM), a $K_{Ca}$ channel inhibitor. In the absence of extracellular $Ca^{2+}$, pre-incubation of the aortic rings with JGH significantly reduced the contraction by PE, suggesting that the relaxant action of the JGH includes inhibition of $Ca^{2+}$ release from intracellular stores. These results indicate that in rat thoracic aorta, JGH may induce vasodilation through ATP sensitive $K^+$ channel activation by prostacyclin production. However, the relaxant effect of JGH may also mediated in part by NO pathways and $Ca^{2+}$ activated $K^+$ channel.

• 대한약리학회지
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• 제29권2호
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• pp.203-212
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• 1993

돼지의 적출뇌동맥에서 저산소 유발 수축반응을 관찰하고 그 기전을 구명하며 저산소가 혈관수축제의 수축반응과 acetylcholine (ACh)의 내피세포 의존성 이완반응에 미치는 영향을 검토코자하여 본 실험을 시행하였다. 내피세포가 존재하는 표본에서는 저산소는 일과성 혈관수축을 일으켰고 산소 재공급시에 일과성 이완 후 수축이 나타나는 이상성 (biphasic) 반응이 관찰되었다. KCI 및 $PGF_{2\alpha}$전처치로 수축된 표본에서 저산소 유발은 추가적 수축반응을 일으켰고, 산소재공급으로 이완반응이 관찰되었다. 내피세포 제거 후 및 nimodipine 또는 indomethacin처리 후 저산소와 산소 재공급에 의한 수축반응은 현저히 감약되었다. 저산소하에서 KCl의 수축반응은 영향받지 않았으나, $PGF_{2\alpha}$와 endothelin (ET)의 수축반응은 현저히 억제되었고 ET수축반응이 저산소에 가장 예민하였다. $PGF_{2\alpha}$와 ET로 수축된 내피세포 존재표본에서 ACh은 용량의존성 이완반응을 일으켰고 이 이완반응은 저산소 하에서 소실되었으며 내피세포 제거표본에서는 ACh의 이완반응이 관찰되지 않았다. $PGF_{2\alpha}$로 처리한 내피세포 존재표본에서 ACh은 cyclic GMP농도를 증가시켰고 이 증가는 저산소하에서 소실되었다. 이상의 성적으로 저산소와 산소 재공급 수축반응은 내피세포 및 calcium의존성이고, prostaglandin계 물질의 유리에 기인한다고 추론하였다.

• Archives of Pharmacal Research
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• 제18권2호
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• pp.129-132
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• 1995

Intravenous administration of O-acetyliervine (an alkaloid from Vertrum album) produced a dose-dependent (10-100 .mu.g/kg) fall in blood pressure and tachycardia in anaesthetized normotensive rats. Pretreatment of animals with propranolol (1mg/kg) abolished these cardiovascular responses of O-acetyljervine similar to that of isoprenaline $(1\mu/ml)$. In isolated tissue experiments, O-acetyljervine $(10-100\mu/ml)$ produced a dose-dependent relaxation of phenylephrine-induced contraction of the rabbit aorta. In guinea-pig spontaneously beating atria, it caused positive inotropic and chronotorpic responses in a dose-dependent fashion $(10-100\mu/ml)$. These responses were abolished in the presence of propranolol $(1\mu/ml)$ similar to that of isoprenaline. These results indicate that O-accetyljervine is adrenoceptor stimulant $(\beta_1\; and\;beta_2)$ like isoprenaline.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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• pp.182-189
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• 1998

Administration of ginsenosides, a mixture of saponin extracted from Panax ginseng, decreased blood pressure in rat. Previous studies have shown that ginsenosides caused endothelium-dependent relaxation, which was associated with the formation of cyclic GMP, suggested that ginsenosides caused release of nitric oxide (NO) from the vascular endothelium. The aim of the present study was to characterize the endothelium-independent relaxation to ginsenosides in the isolated rat aorta. Ginsenosides caused a concentration-dependent relaxation of rat aortic rings without endothelium constricted with 25 mM KCI but affected only minimally those constricted with 60 mM KCI. Ginsenoside Rg3 (Rg3) was a more potent vasorelaxing agonist than total ginsenoside mixture and also the ginsenoside PPT and PPD groups. Relaxation to ginsenosides were markedly reduced by TEA, but not by glibenclamide. Rg3 significantly inhibited Cal'-induced concentration-contraction curves and the "50a2'influx in aortic rings incubated in 25 mM KCI whereas those responses were not affected in 60 mM KCI. Rg3 caused efflux of $"Rb in aortic rings that was inhibited by tetraethy- lammonium (TEA), an inhibitor of Ca"-dependent K'channels, but not by glibenclamide, an inhibitor of AfP-dependent K'channels. These findings indicate that ginsenosides may induce vasorelaxation via activation of Ca2'-dependent K'channels resulting in hyperpolarization of the vas- cular smooth muscle with subsequent inhibition of the opening of voltage-dependent Caf'channels. These effects could contribute to explain the red ginseng-associated vasodilation and the beneficial effect on the cardiovascular system.

• 대한약리학회지
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• 제11권2호
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• pp.41-46
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• 1975

The isolated strips of tortoise intestine are evaluated as a test organ for bioassay of prostaglandin $E_1$. This preparation responded highly sensitively to $PGE_1$ and $PGE_2$ in picogram concentration range. The mean slope and the value of precision index among the doses of 0.1, 0.3 and 0.5ng/ml in final concentration were 37.7 and 0.143, respectively. And this was relatively insensitive to different prostaglandins; $E_1/E_2{\gtrsim}1$, $E_1/A_2{\sim}50$ and $E_1/F_{2\alpha}{\sim}100$, and showed the dual responses to 5-hydroxytryptamine and histamine; initial contraction followed by relaxation. The dose-ratio inducing the relative equal contraction height for $PGE_1$, acetylcholine, caerulein, angiotensin and barium chloride was 0.4 : 50 : 25 : 10 : 100 in this order. These results suggest that the intestinal strips of the tortoise are suitable for bioassay of prostaglandin $E_1$ and $E_2$ between the doses of 0.1 and 1.0 ng/ml level in the tissue extracts.

• 한국동물위생학회지
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• 제18권2호
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• pp.177-181
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• 1995

The effects of histamine were investigated on the uterine smooth muscle motility in the pig. The results were summarized as fellows : 1. Histamine caused the contraction of the porcine uterine smooth muscle and the contractile responses increased between the concetration of histamine $10^{-8}$ and $10^{-5}$ M with a dose-dependent manner. 2. The contractile response Induced by histamine ($10^{-6}$ M) was completely blocked by pretrevatment with $H_1$-histaminergic receptor blocker, pyrilamine($10^{-6}$ M) 3. The contractile response induced by histamine($10^{-6}$ M) was increased by pretreatment with $H_2$-histaminergic receptor blocker, cimetidine($10^{-6}$ M) From these results, it was concluded that the effects of uterine smooth muscle by histamine were the contraction mediated by $H_1$-histaminergic receptor and the relaxation mediated by $H_2$-histaminergic receptor in pig.

• 한국수산과학회지
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• 제37권6호
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• pp.445-454
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• 2004

A search for contraction and relaxation responses on the smooth muscles, antimicrobial and antioxidant activity in different body parts of 4 freshwater fish and 4 marine fish were conducted. The four freshwater fish studied were Sarotherodon niloticus (tilapia), Channa arus (snake head), Cyprinus carpio (Israel carp) and Siluru osotus (catfish), and the four marine fish were Scyliorhinus torazame (tiger shark), Ateiepus japonicus (tadpole fish), Mugil cephalus (gray mullet) and Thamnaconus modestus (file fish). Frozen samples were extracted with distilled water containing $1{\%}$ acetic acid. Antimicrobial activity against Bacillus subtilis and Eschrrichia coli was detected in extracts from several tissues in all species tested. Relatively high antimicrobial activity could also be detected in the bile extracts from C. carpio, M. cephalus, and T. modestus. Contraction and relaxation responses on smooth muscles could be detected in all species tested, especially in the intestine extracts. Antioxidant activity was also detected in extracts from several tissues in all species tested, while in the extracts from S. osotus, excluding livers and spleens, no antioxidant activity was detected. Results from this study suggest that fish are a potential source for the discovery of novel bioactive materials.

• 생명과학회지
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• 제13권5호
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• pp.634-641
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• 2003

외부에서 가해진 비소 스트레스가 내피유무에 따른 흰쥐 대동맥의 수축력 증가와 이완반응에 미치는 영향을 알아보고자 본 실험을 실시하였다. 혈압의 측정은 생리기록계를 이용하였고, 내피 유무에 따른 혈관의 수축력은 Organ bath에 조직을 걸고 자동조절 생리기록계를 이용하여 측정하였다. 중추신경계를 파괴시킨 흰쥐의 생체 내 실험에서 비소처리로 vasopressin과 phenylephrine에 의한 혈관 수축력은 대조군에 비해 각각 19.1%와 46.6%로 대동맥의 혈압은 상승되었다. 0, 0.5, 1, 2 및 4 mM As을 처리한 적출 대동맥 실험에서 phenylephrine $(10^{-6}M)$을 가했을 때 5시간까지는 혈관 수축력의 변화가 미미했으나 8시간째 비소 처리군은 대조군에 비해 39% 증가된 값을 보여 수축력이 더욱 유의하게 증가되었다. 내피 제거 시 저농도 비소처리에서 다소 신속한 수축반응을 보였으나 고농도 비소 처리시에는 내피유무에 따른 차이가 유의적이지 않았다. 이완제 sodium nitroprusside와 acetylcoline를 처리했을 때 대조군에 비해 다소 증가된 이완력을 보였고, 시간경과에 따라 내피 비의존적인 nitroprusside와 달리 내피 의존적인 acetylcholine에서 이완력이 대조군에 비해 다소 촉진되었다. 이상의 결과에서 4 mM As처리시 혈관의 수축력은 증가되었으나 내피유무에 따른 차이는 유의적이지 않았고, 내피가 혈관의 이완력을 다소 촉진시킨 것으로 나타났다. 결론적으로 비소처리한 혈관은 내피유무와 무관하게 수축력이 증가되어 장기간 고농도 비소에 노출 시 고혈압을 유발할 우려가 있을 것으로 여겨진다.