• Environmental Analysis Health and Toxicology
• /
• 제29권
• /
• pp.10.1-10.6
• /
• 2014

Objectives Cigarette smoking had been recorded as the main cause of impaired endothelium-dependent vasodilation in smokers by reducing nitric oxide (NO), a production of endothelial nitric oxide synthase (eNOS). However, the mechanism of NO impairment via eNOS activity is unclear until now. In this study, cell passage is suggested to be a relevant factor to eNOS expression under cigarette smoking stress. Methods Bovine aortic endothelial cells (BAECs) were chosen as the research subject with passages ranking from 6 to 9 (6P to 9P). After exposure of cigarette smoking extract (CSE) solution, MTT assay and Western blot method were performed to check the cell viability as well as eNOS protein concentration. In these experiments, four concentrations of CSE at 0.5, 1, 2, and 4% were selected for treatment. Results Our results showed that cells almost died at 4% of CSE. Besides, eNOS protein mass had a linear decrease under the increase of CSE concentration. In addition, the effect of CSE on eNOS expression was dissimilar between different passages. Conclusions This study indicated that CSE had effect on both cell viability and eNOS expression. Besides, a reduction in protein mass was matched with the decrease of cell viability due to CSE tress. Last but not least, the response of eNOS protein to different concentration of CSE at different passages was disparate, making the hypothesis about cell passage related inhibition of eNOS caused by CSE solution.

• 대한약리학회지
• /
• 제15권1_2호
• /
• pp.45-56
• /
• 1979

With a view to searching after a new antihypertensive or hypotensive agents in the botanical crude plants, authors intended to reevaluate several natural products caltivated in Korea. This experiment was undertaken to compare pharmacogical actions of Machilus thunbergii Siebold et Zuccarini with those of Magnolia obovata Thunberg in anesthetized rats and in normal mice. Machilus thunbergii Sieb. et Zucc., a tree belonging to the Lauraceae family, is caltivated at Ull-ung Do, and their cortecies have been used as folk medicine mingled with those of Magnolia obovata Thunberg. These two cortecies have teen also applied in chinese medicine, it was advocated that these cortecies exerted good therapeutic effects on gastritis, convulsive abdominal pain, nausea, vomiting and urinary tract disorders. Therefore, we intended to determine the pharmacological action of two palnt of different family each other, especially their effects on blood pressure and heart rate, and also their mechanism of action were observed. We studied their action with extracts of hexane(MTHE), ether(MTEE), methanol(MTME) and water(MTWE) from Machilus thunhergii Sieb. et Zucc., and also fractionations of methanol(MOME), chloroform(MOCE) and water(MOWE) from Mapolia obovata Thunberg. The results of this experiment were as follows; 1) MTME, when intravenously administered to rats, elicited the significant hypotensive responses dependent on the administered dosage. 2) MOWE was also exhibited the hypotensive effect dependent on the treated dose. 3) Depressor effect of MTME was blocked by pretreatment with hexamethonium. 4) The hypotensive response of MOWE was blocked by pretreatment with hexamethonium or hrdralazine. 5) HTME and MOWE were also observed the anticonvulsive effect and sedative effect. These results suggested that MTME may induce the hypotensive response via central sympathetic effect, but the site of action in brain are not clarified, and the hypotensive effect of MOWE may be due to dual mechanism of central sympathetic action and direct vasodilation of blood vessel.

• Environmental Analysis Health and Toxicology
• /
• 제15권3호
• /
• pp.69-80
• /
• 2000

ADP-rubosylation may be involved in the process of macrophage activation. Nitric oxide (NO) has emerged as an important intracellular and interacellular regulatory molecule with function as diverse as vasodilation, neural communication or host defense. NO is derived from the oxidation of the terminal guanidino nitrogen atom of L-arginine by the NADPH -dependent enzyme, nitric oxide synthase (NOS) which is one of the three different isomers in mammalian tissues. Since NO can exert protective or regulatory functions in the cell at a low concentration while toxic effects at higher concentrations, its role may be tightly regulated in the cell. Therefore, this paper was focused on signal transduction pathway of NO synthesis, role of endogenous TGF-$\beta$ in NO production. effect of NO on superoxide formation. Costimulation of murine peritoneal macrophages with interferon-gamma (IFN-γ) and phorbol 12-myristate 13-acetate (PMA) increased both NO secretion and mRNA expression of inducible nitric oxide synthase (iNOS) when PMA abolished costimulation. Pretreatmnet of the cells with PMA abolished costimuation effects due to the depletion of protein kinase C (PKC) activities . The involvement of PKC in NO secretion could be further confirmed by PKC inhibitor, stauroprine, and phorbol ester derivative, phorbol 12,13-didecanoate. Addition of actinomycine D in IFN-γ plus PMA stimulated cells inhibited both NO secretion and mRNA expression of iNOS indication that PMA stabilizes mRNA of iNOS . Exogenous TGF-$\beta$ reduced NO secretion in IFN -γ stimulated murine macrophages. However addition of antisense oligodeoxynucleotide (ODN) to TGF-$\beta$ to this system recovered the ability of NO production and inhibited mRNA expression of TGF-$\beta$. ACAS interactive laser cytometry analysis showed that transportation of FITC -labeled antisense ODN complementary to TGF-$\beta$ mRNA could be observed within 5 min and reached maximal intensity in 30 min in the murine macrophage cells. NO released by activated macrophages inhibits superoxide formation in the same cells . This inhibition nay be related on NO-induced auto -adenosine diphosphate (ADP) -ribosylation . In addition, ADP-ribosylation may be involved in the process of macrophage activation .

• 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.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권6호
• /
• pp.621-628
• /
• 2016

Hypertension can be caused by various factors while the predominant causes include increase in body fluid volume and resistance in the circulatory system that elevate the blood pressure. Consumption of probiotics has been proven to attenuate hypertension; however, the effect is much strain-dependent. In this study, a newly isolated Lactobacillus casei (Lb. casei ) strain C1 was investigated for its antihypertensive properties in spontaneously hypertensive rats (SHR). Lactic acid bacteria (LAB) suspension of 11 log colony-forming unit (CFU) was given to SHR (SHR+LAB, n=8), and phosphate buffer saline (PBS) was given as a control in SHR (SHR, n=8) and in Wistar rats as sham (WIS, n=8). The treatment was given via oral gavage for 8 weeks. The results showed that the weekly systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and aortic reactivity function were remarkably improved after 8 weeks of bacterial administration in SHR+LAB. These effects were mostly attributed by restoration of wall tension and tensile stress following the bacterial treatment. Although not statistically significant, the level of malondialdehye (MDA) in SHR+LAB serum was found declining. Increased levels of glutathione (GSH) and nitric oxide (NO) in SHR+LAB serum suggested that the bacterium exerted vascular protection through antioxidative functions and relatively high NO level that induced vasodilation. Collectively, Lb. casei strain C1 is a promising alternative for hypertension improvement.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권2호
• /
• pp.575-579
• /
• 2016

The aim of this research is to determine the characteristics of endothelial factors and the hemostatic system conditions with malignant neoplasms patients, which were exposed to ionizing radiation. Total number of examined people is 223, 153 of them are patients with gastrointestinal tract oncopathology. The article presents the results of the analysis of numerical indicators of endothelial condition and platelet hemostasis of patients, who had cancer. They lived in the regions of Kazakhstan, subjected to contamination of radionuclides as a result of nuclear weapons tests, which took place in this region from 1949 to 1989. These results then were compared to cancer patients and healthy individuals with no radiation risk. The study revealed the presence of higher levels of endothelial dysfunction and following trigger of the hemostatic system in patients with malignant tumors of the gastrointestinal tract. In particular, the defined high degree of endothelial dysfunction include endothelium-dependent vasodilation, content desquamated endothelial cells in peripheral blood and von Willebrand factor. These indicators have a clear correlation with the degree of disorder of studied parameters of the hemostasis, which can cause the development of thrombotic complications.

• Journal of Nutrition and Health
• /
• 제38권1호
• /
• pp.30-39
• /
• 2005

The effects of different concentrations of estrogen supplementation to mature female rats or estrogen supplementation to ovariectomized rats on cyclooxygenase-2 (COX-2) expression, PGE$_2$ production and mapkinases expression were investigated in experimentally induced atherogenic rats with feeding a high fat. high cholesterol diet. In the first experiment using 48-week old mature rats, the supplementation of three different levels of estrogen was compared to the basal diet. The high concentration of estrogen supplementation induced the marked up-regulation of COX-2 protein and the increase in plasma PGE$_2$ production and this seems to be followed by the up-regulation of p38 among mapkinases. The regulation of bax showed in a reverse trend of COX-2 in heart tissues of mature female rats. In the second ex-perimental system, female Sprague-Dawley rats were bilaterally ovariectomized; sham-operated animals were used as controls. Three weeks later, the animals were supplied with basal diet to sham-operated control group and ovariectomized control group, and estrogen supplemented diet to ovariectomized group for an eight-week experimental period. In a group supplemented with a medium dose of estrogen, COX-2 expression was up-regulated. This up-regulation was accompanied by the elevated expression of pERK1/2. Bax was increased in estrogen-fed animals indicating bax might be involved in estrogen feeding state in ovariectomized rats. Further investigations on the relationship between COX-2 and biological activities such as vasodilation by estrogen are required in in vivo system of female rats at the various physiological states.

• Safety and Health at Work
• /
• 제6권3호
• /
• pp.256-262
• /
• 2015

Background: Heart attack is the most common cause of line-of-duty death in the fire service. Daily aspirin therapy is a preventative measure used to reduce the morbidity of heart attacks but may decrease the ability to dissipate heat by reducing skin blood flow. Methods: In this double-blind, placebo-controlled, crossover study, firefighters were randomized to receive 14 days of therapy (81-mg aspirin or placebo) before performing treadmill exercise in thermal-protective clothing in a hot room [$38.8{\pm}2.1^{\circ}C$, $24.9{\pm}9.1%$ relative humidity (RH)]. Three weeks without therapy was provided before crossing to the other arm. Firefighters completed a baseline skin blood-flow assessment via laser Doppler flowmetry; skin was heated to $44^{\circ}C$ to achieve maximal cutaneous vasodilation. Skin blood flow was measured before and after exercise in a hot room, and at 0 minutes, 10 minutes, 20 minutes, and 30 minutes of recovery under temperature conditions ($25.3{\pm}1.2^{\circ}C$, $40.3{\pm}13.7%\;RH$). Platelet clotting time was assessed before drug administration, and before and after exercise. Results: Fifteen firefighters completed the study. Aspirin increased clotting time before and after exercise compared with placebo (p = 0.003). There were no differences in absolute skin blood flow between groups (p = 0.35). Following exercise, cutaneous vascular conductance (CVC) was $85{\pm}42%$ of maximum in the aspirin and $76{\pm}37%$ in the placebo groups. The percentage of maximal CVC did not differ by treatment before or after recovery. Neither maximal core body temperature nor heart rate responses to exercise differed between trials. Conclusion: There were no differences in skin blood flow during uncompensable heat stress following exercise after aspirin or placebo therapy.

• 대한수의학회지
• /
• 제43권4호
• /
• pp.615-624
• /
• 2003

Vascular smooth muscle relaxation is modulated by an increase in cGMP subsequent to nitric oxide (NO) production by endothelial cells. The effects of cAMP and cGMP phosphodiesterase (PDE) inhibitors were investigated in phenylephrine-precontracted rat aorta rings by using the specific inhibitors of PDE I, III, IV and V as relaxing agents (calmodulin-activated PDE inhibitors, IBMX and $W_7$, type I; cAMP-specific PDE inhibitors, milrinone, type IV; Ro 20-1724, type III and cGMP-specific PDE inhibitor, zaprinast, type V). All the PDE inhibitors produced a concentration-dependent relaxation in the ring with intact endothelium (+E). Except for milrinone, all the PDE inhibitors-induced relaxations were inhibited by removal of extracellular $Ca^{2+}$, $N^G$-nitro-L-arginine, $N^G$-nitro-L-arginine methyl ester, methylene blue (MS) or nifedipine. The specific PDE I and PDE IV inhibitors both produced endothelium-independent relaxations which were inhibited by MS in -E rings. However, zaprinast had no effect in -E rings. Except for milrinone, sodium nitroprusside (a NO donor)-induced relaxation was significantly augmented by all PDE inhibitors in +E rings. The results suggest that I) the vasorelaxant properties of IBMX, $W_7$, Ro 20-1724 and zaprinast are dependent on endothelium or on interaction with $Ca^{2+}$ regulation, 2) each PDE is differently distributed in vascular tissues (endothelial and smooth muscle cells), 3) the vasodilations of PDE inhibitors are due to the increase of cAMP and cGMP formation through inhibition of cAMP- and cGMP-PDE and 4) the vasodilation action of milrinone does not involve in endothelial-cyclic nucleotide system.

• Preventive Nutrition and Food Science
• /
• 제6권1호
• /
• pp.43-50
• /
• 2001

The effects of cardiac ischemia-reperfusion and $\beta$-adrenergic stimulation on metabolic function and energetics were investigated in Lan gendorff-perfused spontaneously hypertensive rat (SHR) hearts. Sarcoplasmic reticulum {TEX}$Ca^{2+}${/TEX}-dependent ATPase and cardiac lactate dehydrogenase (LDH) are additionally studied. The perfusion medium (1.0 mM {TEX}$Ca^{2+}${/TEX}) contained 5 mM glucose(+5 U/L insulin) and 2 mM pyruvate as substrates. Global ischemia was induced by reducing perfusion pressure of 100 to 40 cm {TEX}$H_{2}${/TEX}O, followed by 20 min reperfusin. Isoproterenol (ISO, 1$\mu$M) was infused for 10 min. Coronary vascular resistance and myocardial oxygen consumption ({TEX}$MVO_{2}${/TEX}) of SHR were increased in parallel with enhanced venous lactate during ischemia and reperfusion compared to those of Sprague Dawley (SD) hearts. Although ischemia-induced increase in venous lactate and combined adenosine plus inosine was abolished, coronary vasodilation produced in SD during reperfusion. In SHR, depressed reactive hyperemia was associated with a fall in cardiac ATP and CrP/Pi ratio and a rise in intracellular lactate/Pyruvate ratio. On the other hand, ISO produced coronary functional hyperemia and an increase in {TEX}$MVO_{2}${/TEX}. However, these responses were less than those in SHR hearts. The ATPase activity of SHR was attenuated in free {TEX}$Ca^{2+}${/TEX} concentrations used under basal condition and with ISO compared to that of SD. Venous lactate output and cardiac LDH activity were augmented in SHR as influenced by ISO. These results demonstrate that coronary reactive and functional hyperemia was dpressed in SHR, which cold be explained by alterations in the cytosolic phosphorylation potential and the cytosolic redox state manipulated by LDH, and by abnormal free calcium handling.