• Biomolecules & Therapeutics
• /
• 제26권4호
• /
• pp.374-379
• /
• 2018

In this study, we investigated the effects of pelargonidin, an anthocyanidin found in many fruits and vegetables, on endothelium-independent vascular contractility to determine the underlying mechanism of relaxation. Isometric contractions of denuded aortic muscles from male rats were recorded, and the data were combined with those obtained in western blot analysis. Pelargonidin significantly inhibited fluoride-, thromboxane A2-, and phorbol ester-induced vascular contractions, regardless of the presence or absence of endothelium, suggesting a direct effect of the compound on vascular smooth muscles via a different pathway. Pelargonidin significantly inhibited the fluoride-dependent increase in the level of myosin phosphatase target subunit 1 (MYPT1) phosphorylation at Thr-855 and the phorbol 12,13-dibutyrate-dependent increase in the level of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation at Thr202/Tyr204, suggesting the inhibition of Rho-kinase and mitogen-activated protein kinase kinase (MEK) activities and subsequent phosphorylation of MYPT1 and ERK1/2. These results suggest that the relaxation effect of pelargonidin on agonist-dependent vascular contractions includes inhibition of Rho-kinase and MEK activities, independent of the endothelial function.

• The Korean Journal of Physiology and Pharmacology
• /
• 제3권6호
• /
• pp.571-578
• /
• 1999

This study evaluated the effects of PKC activation using phorbol 12-myristate 13-acetate (PMA) and PKC inhibition using the isoquinoline sulfomide derivative H-7 on hemodynamics and glucoregulation in the isolated perfused rat liver. Livers were isolated from fed male Holtzman rats and perfused with Krebs Ringer bicarbonate solution under a constant flow of 50 ml/min at $35^{\circ}C.$ Portal vein pressure, glucose and lactate concentrations in the medium and oxygen consumption rates were continuously monitored by a Grass polygraph, YSI glucose and lactate monitors, and a YSI oxygen monitor, respectively. PMA at concentration of 2 to 200 nM increased the portal vein pressure, glucose and lactate production, but decreased oxygen consumption rate in a dose-dependent fashion. H-7 $(200\;{\mu}M)$ attenuated PMA (50 nM)-induced vasoconstriction $(15.1{\pm}1.36\;vs\;10.56{\pm}1.17\;mmHg),$ glucose production rate $(91.3{\pm}6.15\;vs\;71.8{\pm}2.50\;{\mu}moles/g/hr),$ lactate production rate $(72.4{\pm}6.82\;vs\;53.6{\pm}4.82\;{\mu}moles/g/hr)$ and oxygen consumption rate $(33.7{\pm}1.41\;vs\;27.9{\pm}1.75\;{\mu}l/g/min).$ The effects of PMA were blocked either by addition of verapamil $(9\;{\mu}M)$ or perfusion with $Ca^{2+}-free$ KRB. These results suggest that the hemodynamic and glucoregulatory changes in the perfused rat liver are mediated by protein kinase C activation and require $Ca^{2+}$ influx from the extracellular fluid.

• The Korean Journal of Pain
• /
• 제31권2호
• /
• pp.102-108
• /
• 2018

Background: Nefopam is a non-opioid, non-steroidal analgesic drug with fewer adverse effects than narcotic analgesics and nonsteroidal anti-inflammatory drugs, and is widely used for postoperative pain control. Because nefopam sometimes causes side effects such as nausea, vomiting, somnolence, hyperhidrosis and injection-related pain, manufacturers are advised to infuse it slowly, over a duration of 15 minutes. Nevertheless, pain at the injection site is very common. Therefore, we investigated the effect of warmed carrier fluid on nefopam injection-induced pain. Methods: A total of 48 patients were randomly selected and allocated to either a control or a warming group. Warming was performed by diluting 40 mg of nefopam in 100 ml of normal saline heated to $31-32^{\circ}C$ using two fluid warmers. The control group was administered 40 mg of nefopam dissolved in 100 ml of normal saline stored at room temperature ($21-22^{\circ}C$) through the fluid warmers, but the fluid warmers were not activated. Results: The pain intensity was lower in the warming group than in the control group (P < 0.001). The pain severity and tolerance measurements also showed statistically significant differences between groups (P < 0.001). In the analysis of vital signs before and after the injection, the mean blood pressure after the injection differed significantly between the groups (P = 0.005), but the heart rate did not. The incidence of hypertension also showed a significant difference between groups (P = 0.017). Conclusions: Use of warmed carrier fluid for nefopam injection decreased injection-induced pain compared to mildly cool carrier fluid.

• 한국산학기술학회논문지
• /
• 제14권12호
• /
• pp.6340-6345
• /
• 2013

본 연구는 열 자극으로 유도된 신경성 염증 상태에서 혈류량의 변화와 histamine의 치수혈류 조절에 관해 유기적 관계를 연구함으로써 치수혈류 조절기전을 밝히고자 하였다. 연구방법은 열 마리의 고양이를 전신마취 하에 사용되었으며, 치수혈류의 변화는 레이저 도플러 측정계(Periflux 4001, Stockholm, Sweden)을 사용하여 측정 하였다. 레이저 도플러 측정하는 프로브는 하악 견치의 치면에 위치하였다. 열 자극은 입력/출력 장치와 열 자극 제어 스크립트 파일을 사용하여 치아에 적용하였다. 열($40-65^{\circ}C$)에 따라 치수 혈류량이 증가를 확인하였으며, $55^{\circ}C$에서 가장 큰 변화가 나타났다. 열 자극의 변화가 없는 $45^{\circ}C$에서 Histamine($5{\mu}g/kg/1ml$)를 치아와 가까운 설 동맥으로 주입 시 열 자극만 처치한 그룹보다 현저한 증가가 나타났다. 본 연구는 열적 자극에 의해 발생된 신경성 염증상태에서 치수혈류 변화와 이에 히스타민의 기능적으로 관여함을 나타내주며, 치아 염증 상태의 기전을 밝힐 수 있는 가능성을 보여준다.

• Journal of Korean Neurosurgical Society
• /
• 제57권1호
• /
• pp.1-5
• /
• 2015

Objective : Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. Methods : The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately $-500{\mu}m$ in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). Results : We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin $PGH_2$. Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. Conclusion : Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models.

• 대한본초학회지
• /
• 제31권3호
• /
• pp.13-22
• /
• 2016

Objectives： Arachidonic acid is control the thromboxane A2 (TXA2) and prostacycline (PGI2) synthesis, TXA2 increase lead to thrombus produced by induces platelet aggregation and vasoconstriction. Angelicae gigantis radix (RAR) is mainly used blood deficiency and stagnation. In previous studies, RAR has been reported that a vasodilating and blood clotting delay effects. In this study, investigate that anti-oxidant and anti-thrombotic effects of RAR by heat-process.Methods： The heated angelicae gigantis radix sample were made by 140, 180, and 220 ℃ and 4, 6, 9 and 12 min using water or 30% ethanol. The anti-oxidant effects were measured by total polyphenol, total flavonoid, DPPH and ABTS radical scavening activation. Anti-thrombotic effect conducted in samples that are determined to be effective through the anti-oxidant experiment such as angelicae gigantis radix roasted 180℃, and 220℃ and angelicae gigantis radix roasted with 30% ethanol 180℃, and 220℃.Results： Anti-oxidant parameters were efficacious in high temperature roasted AR. Also AR and EAR increased a inhibitory activity of FXa compared with RAR. The blood coagulation time of administration groups were significantly increased compare with control group. The TXB2 was significantly decreased in AR and EAR.Conclusions : We confirmed that whether AR and EAR administration has anti-oxidant and anti-thrombotic effect or not. As the results, AR and EAR were improved anti-oxidant effects and blood biochemistry compare with control group. This study provides scientific evidence that AR and EAR are have an anti-oxidant effect and anti-thrombotic effect, it expected that there is no difference between the two.

• Toxicological Research
• /
• 제32권4호
• /
• pp.353-358
• /
• 2016

The generation and collection of cigarette smoke (CS) is a prerequisite for any toxicology study on smoking, especially an in vitro CS exposure study. In this study, the effects on blood and vascular function were tested with two widely used CS preparations to compare the biological effects of CS with respect to the CS preparation used. CS was prepared in the form of total particulate matter (TPM), which is CS trapped in a Cambridge filter pad, and cigarette smoke extract (CSE), which is CS trapped in phosphate-buffered saline. TPM potentiated platelet reactivity to thrombin and thus increased aggregation at a concentration of $25{\sim}100{\mu}g/mL$, whereas 2.5~10% CSE decreased platelet aggregation by thrombin. Both TPM and CSE inhibited vascular contraction by phenylephrine at $50{\sim}100{\mu}g/mL$ and 10%, respectively. TPM inhibited acetylcholine-induced vasorelaxation at $10{\sim}100{\mu}g/mL$, but CSE exhibited a minimal effect on relaxation at the concentration that affects vasoconstriction. Neither TPM nor CSE induced hemolysis of erythrocytes or influenced plasma coagulation, as assessed by prothrombin time (PT) and activated partial thromboplastin time (aPTT). Taken together, CS affects platelet activity and deteriorates vasomotor functions in vitro. However, the effect on blood and blood vessels may vary depending on the CS preparation. Therefore, the results of experiments conducted with CS preparations should be interpreted with caution.

• 한국정보통신학회:학술대회논문집
• /
• 한국해양정보통신학회 2003년도 추계종합학술대회
• /
• pp.860-863
• /
• 2003

산소포화도 측정은 Beer-Lambert's law를 기초로하여 측정 부위(손가락, 귀 등)에 LED를 발광한 후 투과된 적생광과 적외선광 신호가 통과하고 photodetector에서 감지한 후 나타난 두 광의 비율로 계산한다. Pulse oximetry는 이러한 산소포화도를 측정하는 기기인데, 근데 아주 민감하기 때문에 압력이 적절한 조직 혈류로 공급하기 어려울 정도로 아주 낮을 때 펄스를 검출한다. 다시말해서, SpO2는 혈관 수축이나 저혈압에서의 흐르지 않는 동맥혈의 펄싱의 손가락에 의한 O2소모 때문에 감소할 수도 있다. 이러한 점에서 측정 결과시의 한계가 있다. 따라서 본 논문은 SpO2를 측정할 때 어떠한 움직에 의해 나타나는 motion artifact를 최소화하는 알고리즘을 고찰하였다.

• Restorative Dentistry and Endodontics
• /
• 제27권5호
• /
• pp.543-551
• /
• 2002

Nitric oxide (NO) is a small molecule (mol. wt. 30 Da) and oxidative free radical. It is uncharged and can therefore diffuse freely within and between cells across membrane. Such characteristics make it a biologically important messenger in physiologic processes such as neurotransmission and the control of vascular tone. NO is also highly toxic and is known to acts as a mediator of cytotoxicity during host defense. NO is synthesized by nitric oxide synthase (NOS) through L-arginine/nitric oxide pathway which is a dioxygenation process. NO synthesis involves several participants, three co-substrates, five electrons, five co-factors and two prosthetic groups. Under normal condition, low levels of NO are synthesized by type I and III NOS for a short period of time and mediates many physiologic processes. Under condition of oxidant stress, high levels of NO are synthesized by type II NOS and inhibits a variety of metabolic processes and can also cause direct damage to DNA. Such interaction result in cytostasis, energy depletion and ultimately cell death. NO has the potential to interact with a variety of intercellular targets producing diverse array of metabolic effects. It is known that NO is involved in hemodynamic regulation, neurogenic inflammation, re-innervation, management of dentin hypersensitivity on teeth. Under basal condition of pulpal blood flow, NO provides constant vasodilator tone acting against sympathetic vasoconstriction. Substance P, a well known vasodilator, was reported to be mediated partly by NO, while calcitonin-gene related peptide has provided no evidence of its relation with NO. This review describes the roles of NO in dental pulp in addition to the known general roles of it.

• The Korean Journal of Physiology and Pharmacology
• /
• 제18권2호
• /
• pp.95-101
• /
• 2014

Cardiovascular disease is the prime cause of morbidity and mortality and the population ages that may contribute to increase in the occurrence of cardiovascular disease. Arginase upregulation is associated with impaired endothelial function in aged vascular system and thus may contribute to cardiovascular disease. According to recent research, Korean Red Ginseng water extract (KRGE) may reduce cardiovascular disease risk by improving vascular system health. The purpose of this study was to examine mechanisms contributing to age-related vascular endothelial dysfunction and to determine whether KRGE improves these functions in aged mice. Young ($10{\pm}3$ weeks) and aged ($55{\pm}5$ weeks) male mice (C57BL/6J) were orally administered 0, 10, or 20 mg/mouse/day of KRGE for 4 weeks. Animals were sacrificed and the aortas were removed. Endothelial arginase activity, nitric oxide (NO) generation and reactive oxygen species (ROS) production, endothelial nitric oxide synthase (eNOS) coupling, vascular tension, and plasma peroxynitrite production were measured. KRGE attenuated arginase activity, restored nitric oxide (NO) generation, reduced ROS production, and enhanced eNOS coupling in aged mice. KRGE also improved vascular tension in aged vessels, as indicated by increased acetylcholine-induced vasorelaxation and improved phenylephrine-stimulated vasoconstriction. Furthermore, KRGE prevented plasma peroxynitrite formation in aged mice, indicating reduced lipid peroxidation. These results suggest KRGE exerts vasoprotective effects by inhibiting arginase activity and augmenting NO signaling and may be a useful treatment for age-dependent vascular diseases.