• The Korean Journal of Pharmacology
• /
• v.26 no.2
• /
• pp.135-144
• /
• 1990

The vascular responses to the vasoactive drugs were evaluated using aortic ring preparations obtained from propylthiouracil (PTU)-treated rats. The body weights and the levels of serum thyroxine $(T{_4})$ and triiodothyronine $(T{_3})$ were significantly decreased in propylthiouracil-treated rats as compared with those in age-matched control rats. The contractile responses to norepinephrine and potassium and calcium ions were significantly attenuated in aortic rings of PTU-treated rats 4 weeks after when compared with those from age-matched control animals. By the PTU treatment, however, the sensitivity to norepinephrine but not to calcium was decreased while the maximal responses to norepinephrine and calcium were reduced together. The attenuated contractile responses to the vasoconstrictors in PTU-treated rats are ascribed to the decreased ability of the muscle cells to contract. On the other hand, the relaxation responses induced by acetylcholine and histamine (endothelium-dependent relaxants) and isoproterenol and sodium nitroprusside (endothelium-independent relaxants) had tendencies to be augmented in aortic rings of PTU-treated rats when compared with those of age-matched control animals. However, the sensitivities to the endothelium-independent relaxants were different between PTU-treated and control rats whereas those to the endothelium-dependent relaxants were not. These results suggest that the altered vascular responsiveness in the PTU-treated rats seems to be due to the alteration of smooth muslce cells rather than the Influence of endothelium, and that this change is slowly progressive after hypothyroidism is evident.

• The Journal of Internal Korean Medicine
• /
• v.27 no.1
• /
• pp.276-287
• /
• 2006

Background & Objective : The herbal medicine Sojukgunbihwan granule has been used for the treatment of functional dyspepsia, generally categorized as a gastric dysmotility disease. However, its mechanisms are not yet well known. Therefore, the effects of Sojukgunbihwan granules on gastric motility in rats was investigated. Methods : The myoelectrical activity of the gastric smooth muscle was recorded by a bipolar electrode placed at the gastric antrum of rats. The contractile waves were measured for 30 minutes before and after intragastric administration of each solution(normal saline, Pyungwisan 40mg/kg, Sojukgunbihwan granules 60mg/kg) and expressed as the motility index. Gastric emptying was measured by the number of glass beads expelled from the stomach(containing one hundred 1mm glass beads) within an hour after glass beads and test drugs(normal saline, Pyungwisan 40mg/kg, Pyungwisan 120mg/kg, Sojukgunbihwan granules 60mg/kg, Sojukgunbihwan granules 180mg/kg) were administered. In another series of experiments to evaluate the mechanisms of Sojukgunbihwan granules under delayed conditions, the rats were treated with atropine sulfate(1 mg/kg, s.c.), cisplatin(10mg/kg, i.p.), and NAME($N^G$-nitro-L-arginine methyl ester, 75mg/kg, s.c.) respectively. Results : Intragastric administration of Sojukgunbihwan granules increased the myoelectrical activity significantly, gastric motility index rose 25%, and gastric emptying of glass beads was significantly enhanced over a period of 60minutes. Under the delayed gastric emptying induced by atropine sulfate, cisplatin, and NAME, Sojukgunbihwan granules aggravated gastric emptying in the atropine sulfate($5.71{\pm}3.45\;vs\;3.71{\pm}4.42$) and cisplatin($13.86{\pm}3.53\;vs\;5.14{\pm}5.05$, p<0.01) treated groups, but enhanced gastric emptying in the NAME treated group($5.00{\pm}3.21\;vs\;11.71{\pm}5.65$, p<0.05). Conclusions : Results suggest that Sojukgunbihwan granules stimulate gastric motility through cholinergic and 5-hydroxytryptamine 3 receptors. Results are indicative of Sojukgunbihwan as an especially effective remedy in dysmotility-like functional dyspepsia with impaired reservoir functions such as gastric adaptive relaxation.

• The Journal of Internal Korean Medicine
• /
• v.29 no.1
• /
• pp.117-129
• /
• 2008

Background & Objective : Naeso-san(NSS) has been used for the treatment of functional dyspepsia, regarded as a gastric dysmotility disease. A main cause of gastric dysmotility is antral dilatation or antroduodenal uncoordination. Therefore, we investigated the effect of NSS on gastric motility and its mechanism of action, as well as the morphologic changes in antral dilatated rats. Methods : Antral dilatated rats were induced by wrapping a nonabsorbable rubber ring(D:6mm, W:4mm, T:1mm) around the 1st portion of the duodenum for 8 weeks. Then morphologic changes were investigated and compared with normal intact rats before and after 8 weeks. Gastric emptying was measured by administration of normal saline(NS) or NSS in normal intact and antral dilatated rats. In another series of experiments to evaluate the mechanism of NSS under delayed conditions, normal intact rats were treated with atropine sulfate(1mg/kg, s.c.), quinpirole HCl(0.3mg/kg, i.p.), $NAME(N^{G}-nitro-L-arginine$ methyl ester, 75mg/kg, s.c.) and cisplatin(10mg/kg, i.p.), respectively. The myoelectrical activity of the gastric smooth muscle was recorded in normal intact and antral dilatated rats. The contractile waves were measured for 30 minutes before and after administration of each solution(NS, NSS). Results : Body weight gain of antral dilatated rats was significantly lower than that of the controls. Futhermore, we found the thickness of the mucosal and muscular layers and surface area of the stomach increased significantly compared with controls. NSS 278㎎/㎏ improved gastric emptying more than normal saline or NSS 93mg/kg in normal intact(p=0.026) and antral dilatated rats(p=0.03). NSS enhanced gastric emptying significantly in the NAME treated group(p=0.002). NSS 278mg/kg increased the significant postprandial dominant power than that of NS in normal intact rats, whereas there was no statistical significance in antral dilatated rats. Conclusions : NSS stimulates gastric motility through the cholinergic pathway. We expect that pathologic model with antral dilatation can be used as an exprimental tool which is similar to dyspepsia and NSS would be effective especially in dysmotility-like functional dyspepsia with antral dilatation or impaired reservoir functions such as gastric adaptive relaxation.

• Journal of Chest Surgery
• /
• v.29 no.12
• /
• pp.1299-1305
• /
• 1996

The rat thoracic aorta was harvested to determine whether either hyperkalemla or hypothermia impairs the endothelium-dependent re axation of the vascular smooth muscle. Isolated thoracic aorta segments were studied in five groups(n=10 in each group). In group I(control), the isolated aortic seglnents were suspended in organ bath without any intervention. In group ll(endotheilum removAl). the endothelium of the aortic segment was removed by gentle rubbing of the intimal surface with a pair of forceps. In group III(457), IV(4mST), and V(3757), the aortic segments were exposed for 45minutes to 4$^{\circ}C$ St. Thomas hospital cardioplegic solution(57 : NaCl, 144.3; KCI, 19.6, MgCl:, 15.7 : CaCl, 2.2 mmol/L).4$^{\circ}C$ modified St. Thomas hospital cardioplegic solution(NaCl, 144.3 : KCI. 140.0 : MgCl:, 15.7; CaCl:. 2.2 mmol/L). and 37$^{\circ}C$ 57, before suspending in the organ bath, respectively. Then, aorta segments were suspended in organ baths(physiologic salt solution, 37$^{\circ}C$, 95% oxygen and 5% carbon dioxide) for Isometric tension recording. The vasodilatation to acetylcholine (10-2 to 10-2mol/L) was not impaired in control, 457, 4mST, nd 3757 groups. The vasodilatation to acetylcholine was impaired in endothelium removal group. The vasodilatation to sodium nitroprusslde (10-2 to 10-2 mol/L) was not impaired in all groups. In conclusion, both hyperkalemia and hypothermia do not alter irreversibly the function of the rondothelium of the thoracic aorta of the rat.

• The Korea Journal of Herbology
• /
• v.28 no.4
• /
• pp.83-92
• /
• 2013

Objectives : Lespedeza Cuneata has been used to treat leukorrhea, asthma, stomach pain, diarrhea, acute mastitis, in Korean traditional medicine. According to recent studies, Lespedeza Cuneata has antioxidation, hypoglycemia, cell protective, insulin secretion, whitening, corpora cavernosa smooth muscle relaxation and antimicrobial activities, but it has been rarely conducted to evaluate the immuno-biological activity. The present study was examined to evaluate the anti-inflammatory effects of the Lespedeza Cuneata MeOH extract (LCE) in vivo and in vitro. Methods : In vitro, inflammatory mediators, such as cytokines, nitric oxide and prostaglandin $E_2$ were detected after the addition of LPS with or without LCE in Raw 264.7 macrophage cell line. In vivo, anti-edema effect of LCE was determined in the carrageenan-induced paw edema model in rats. Results : In vitro assay, LCE decreased release of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) via suppression of iNOS and COX-2 expression. LCE inhibited the phosphorylation of $I{\kappa}B$ indicating the suppression of NF-${\kappa}B$ pathway. In vivo assay, LCE significantly inhibited the formation of paw edema induced by carrageenan injection in rats. LCE effectively inhibited increases of hind paw skin thickness and inflammatory cell infilterations. Conclusion : These findings demonstrate that LCE has inhibitory effect on inflammatory mediators in LPS-activated Raw 264.7 cells and on paw edema in carrageenan-stimulated rats, showing the possibility of anti-inflammatory use of Lespedeza Cuneata.

• The Korean Journal of Pharmacology
• /
• v.26 no.1
• /
• pp.13-23
• /
• 1990

Methylene Blue (MeB) and gentian violet $(10^{-6}{\sim}10^{-4}\;M)$ produced contractions in isolated thoracic aortic preparations of rabbits in a dose-dependent fashion, while other dyes, evans blue and eosine yellowish, did not affect the basal tension in the same range of doses. Porcine mesenteric arterial rings also responded to MeB with dose-dependent contractions. Single dose of $10^{-4}$ M MeB produced a biphasic response: contraction followed by relaxation. The contraction developed slowly within $2{\sim}4$ min and peaked in about 20 minutes and then slowly relaxed to the basal level. Tyramine $(10^{-4}\;M)$ also induced contraction but it developed faster and was more persistent than that of MeB. While the tyramine-induced tension was reproducible, the MeB-induced one wat not reiterable until 3 to 5 hours after washing out the MeB. Adding $10^{-4}$ M MeB further potentiated the contraction induced by $10^{-4}$ M tyramine. However, the MeB contraction was not affected by further addition or tyramine. Both tyramine- and MeB-induced tensions were abolished or significantly inhibited by pretreatment with various drugs acting on the sympathetic nervous system. The tyramine-induced tension was more sensitive to guanethidine and 6-hydroxydopamine than the MeB-induced tension, while the latter was more sensitive to $Ca^{2+}-free$ PSS and reserpine. But they have similar sensitivity to prazosin. The MeB-induced tension was significantly inhibited but not abolished by 6-hydroxydopamine pretreatment. However, either tyramine or 6-hydroxydopamine could not affect the basal tension of the ring that MeB once had been tested. These results suggest that MeB-induced contractions of rabbit thoracic aorta and porcine mesenteric artery result from a release of endogenous norepinephrine from adrenergic nerve endings and are dependent in part on extracellular calcium, and that the potency of MeB to release or to deplete norepinephrine is greater than that of either tyramine or 6-hydroxydopamine.

• Clinical and Experimental Pediatrics
• /
• v.48 no.7
• /
• pp.772-778
• /
• 2005

Purpose : Kawasaki disease(KD) is a systemic panvasculitis that causes coronary artery lesions. KD is accompanied by immunoregulatory abnormalities. Nitric oxide(NO) can induce relaxation of blood vessels by activating guanylate cyclase in smooth muscle cells and high levels of NO may result in coronary artery lesions. We investigated tumor necrosis factor$(TNF)-{\alpha}$ and NO production before and after intravenous immunoglobulin(IVIG) therapy to study the roles of NO and $TNF-{\alpha}$ in KD with coronary artery lesions. Methods : Serum levels of NO and $TNF-{\alpha}$ were measured in 24 patients with KD(group I, eight patients with normal coronary artery; group II, 16 patients with coronary artery lesions) and 23 controls(group III, 13 afebrile controls; group IV, 10 febrile controls). Blood samples from each subject were drawn before and after IVIG therapy and in the convalescent stage. Serum concentrations of NO and $TNF-{\alpha}$ were measured by enzyme linked immuno sorbent assay. Results : The NO levels before IVIG therapy were significantly higher in group II than in group I, group III and group IV. After IVIG therapy the levels of NO were significantly higher in group I and group II than in group III. The $TNF-{\alpha}$ levels before IVIG therapy were significantly higher in group I and group II than in group III. The serum $TNF-{\alpha}$ and NO levels were higher before IVIG therapy and decreased through the convalescent stage in KD patients. In the acute stage of KD patients with coronary artery lesions, serum NO levels significantly correlated with white blood cells (r=0.43, P<0.05). Conclusion : The serum concentration levels of $TNF-{\alpha}$ and NO were abnormally high in KD patients and NO concentrations were statistically higher in the KD patients with coronary artery abnormalities than those without coronary abnormality during the early stage of the KD. These results suggest NO may be involved in the development of coronary artery lesions.

• The Korean Journal of Physiology
• /
• v.22 no.2
• /
• pp.189-206
• /
• 1988

The effects of ouabain on the contractile and electrical activities were investigated in the isolated preparations of guinea-pig taenia coli, and compared with those of vanadate. Spontaneous contractions were recorded with force transducer, and electrical activites were measured by use of suction electrode, or single sucrose-gap technique. The contractions were induced by the electrical stimulation for 5 seconds every 1 minute with alternating current (60 Hz, 3.0 V/cm) through the platinum electrodes located in parallel with the long axis of the preparation. All experiments were performed in tris-buffered Tyrode solution which was aerated with $100%{\;}O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) Responses of spontaneous contractions to ouabain were concentration-dependent; $10^{-7}M$ ouabain caused a rise of basal tone. Above the concentration of $10^{-6}M$ ouabain, an initial increase followed by a decrease in tension was observed. 2) A continuous spike discharge was induced by the administration of $10^{-7}M$ ouabain. Above $10^{-6}M$ ouabain, a transient initial increase followed by a decrease in spike frequency and amplitude was produced, and finally membrane potential was sustained at a certain level without a spike discharge. 3) The characteristic response to $10^{-7}M$ ouabain was not blocked by the pretreatment with $10^{-7}M$ atropine. 4) The electrically induced contractions were completely suppressed at the concentration of $2{\times}10^{-7}M$ ouabain. These contractions were blocked more rapidly in paralled with the increase in ouabain concentration. 5) Effects of vanadate on the spontaneous activities were quite different from those of ouabain; $10^{-6}M$ vanadate increased the amplitude of contractions and $10^{-5}M$ vanadate increased slightly both amplitude and frequency of spontaneous contractions. $10^{-4}M$ vanadate showed irregular phasic contractions superimposed on the increased basal tone. 6) $10^{-5}M$ vanadate depolarized the membrane potential and shortened the interval between the bursts of spike discharge, whereas $10^{-4}M$ vanadate induced continuous spike discharge with membrane depolarization. 7) Vanadate caused a characteristic inhibitory response to the contractions induced by electrical stimulation; An initial rapid inhibition of tension development and then gradual recovery to a certain level. From the above results, the following conclusions could be made: 1) The rise of basal tone at $10^{-7}M$ ouabain is due to continuous spike discharge without a silent period. The continuous spike discharge is likely to be associated with a slight membrane depolarization caused by the blockage of Na pump. 2) The biphasic response induced by above $10^{-6}M$ ouabain seems to occur by the different mechanisms. The initial increase in tension is associated with depolarization along with an increase in spike frquency, whereas the subsequent relaxation occurs through a non-electrical mechanism. 3) The characteristic response to $10^{-7}M$ ouabain is resulted not from the action on intrinsic nerve terminal, but from its direct action on the membrane of smooth muscle cells. 4) The phasic contractions superimposed on the increased basal tone at the concentration of $10^{-4}M$ vanadate is resulted from the continuous spike discharge with membrane depolarization, of which mechanism remains unknown. 5) The inhibitory action of ouabain on the electrically induced contractions suggests that the increasein intracellular Na in some way inhibits the electrically induced $Ca^{2+}$ influx. The mechanism of vanadate action on the induced contractions remains unknown.

• Tuberculosis and Respiratory Diseases
• /
• v.45 no.1
• /
• pp.77-89
• /
• 1998

Background: Genetic and environmental factors are known to affect the incidence and severity of asthma. Stimulation of $\beta_2$-Adrenergic Receptor ($\beta_2$AR) results in smooth muscle relaxation, leading to decrease in resistance of airflow. The gene encoding the $\beta_2$AR has recently been seguenced. The $\beta_2$AR genotype at the polymorphic loci of codons 16, 27, 34, and 164 was known to cause changes in the amino acids. The relationships between the structure of the $\beta_2$AR and its functions are being elucidated. Purpose : The gene encoding the $\beta_2$AR was carried out to assess the frequency of polymorphisms in bronchial asthma, to determine wheather these polymorphisms have any relation to the severity, or nocturnal symptoms in bronchial asthma. Methods: The subjects studied were 103 patients with bronchial asthma, which consisted of 30 mild episodic, 32 mild persistent, 17 moderate, and 24 severe asthma patients. The polymorphisms of the $\beta_2$AR gene were detected by mutated allele specific amplification (MASA) method at the codons 16,27,34, and 164. Results: The most frequent polymorphism was arginine 16 to glycine. The other two polymorphisms, valine 34 to methionine and glutamine 27 to glutamic acid occured in 11 and 6 patients respectively. The polymorphism of threonine 164 to isoleucine was not found in our enrolled patients. The homozygous polymorphism of $\beta_2$AR gene was found in only arginine 16 to glycine (12.6%). The heterozygous polymorphisms of $\beta_2$AR gene were in arginine 16 to glycine, valine 34 to methionine, and glutamine 27 to glutamic acid, as 65.1 %,10.7%, and 5.8% respectively in asthma patients. The presence of agrginine 16 to glycine heterozygous or/and homozygous polymorphism was associated in severe asthma (p=0.015), but there was no association between the other three polymorphisms and the severity of asthma. The frequency of the $\beta_2$AR gene polymorphisms was no relation in nocturnal asthma as compared with non-nocturnal asthma. Conclusion: The arginine 16 to glycine polymorphism of the $\beta_2$AR gene is the most frequently found in asthma patients and association with severe asthma. But there was no association between the polymorphism of the $\beta_2$AR gene and nocturnal asthma.