• The Korean Journal of Physiology
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• v.29 no.1
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• pp.51-59
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• 1995

This study was designed to test whether or not 1) ischemia-reperfusion attenuates endothelium-dependent relaxation of coronary arteries and 2) preconditioning protects the arterial endothelium from ischemia-reperfusion injury. In anesthetized open chest rabbits, branches of the left circumflex artery were exposed to different combinations of the experimental conditions; ischemia (15 minutes), ischemia (15 minutes)-reperfusion (10 minutes), preconditioning ischemia, and pre-conditioning fellowed by ischemia-reperfusion. Preconditioning consisted of 3 occlusions of 2-min duration, each followed by n 5-min reperfusion. Rings of the artery exposed to the experimental condition and of normal left anterior descending coronary artery were prepared and suspended for isometric force measurement in organ chambers containing Krebs Ringer bicarbonate solution. The rings were contracted with 29.6 mM KCI. Ischemia alone did not attenuate endothelium-dependent relaxation by acetylcholine. However, ischemia-reperfusion significantly impaired endothelium-dependent relaxation. Endothelium-independent relaxation by sodium nitroprusside was not impaired by ischemia-reperfusion and the constrictive response to acetylcholine was not altered in reperfused rings without endothelium, compared with control rings. Arterial rings exposed to preconditioning followed by ischemia-reperfusion exhibited impaired endothelium-dependent relaxation by acetyl-choline. However, although preconditioning not fellowed by ischemia-reperfusion, attenuated endothelium-dependent relaxation at low concentrations of acetylcholine, the magnitude of the impairment by preconditioning followed by ischemia-reperfusion was significantly less than that of the impairment by ischemia-reperfusion alone. These data demonstrate that ischemia-reperfusion significantly attenuates endothelium-dependent relaxation by producing endothelial dysfunction and preconditioning Protects the endothelium of coronary arteries from ischemia-reperfusion injury.

• Journal of Pharmaceutical Investigation
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• v.8 no.1
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• pp.17-26
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• 1978

Effects of Acanthopanax EtOH Extract (AEE) on the serum total cholesterol content of normal and cholesterol administered rabbits were investigated as a series of studies on pharmacological action, especially blood pressure to Korean Acanthopanax. AEE was administered orally(100mg/kg/day) and subcutaneously (30mg/kg/day) in both normal and cholesterol administered rabbits for 36 days. In this experiment the results obtained by comparing with values of the corresponding control group were as follows; 1) In the normal rabbits, long-term administration of AEE for 36 days did not entirely influence the serum total cholesterol content measured at 12th, 24th and 36th day and also not affect the original blood pressure and changes of blood pressure to norepinephrine, angiotensin and acetylcholine recorded at 36th day. 2) In the cholesterol administered rabbits, hypercholesteremia was induced by oral administration of cholesterol(300mg/kg/day) with feed. The rise rate of serum total cholesterol content was not modified at 12th day, whereas significantly inhibited at 24th and 36th days after begining this examination in both groups orally and subcutaneously administered AEE. Original blood pressure was declined and depressor action of acetylcholine was weakened in only group admininstered orally AEE of cholesterol-fed groups. Changes of blood pressure to norepinephrine and angiotensin in these all cholesterol-fed groups, and to acetylcholine in subcutaneous group of these cholesterol-fed groups were not affected significantly by AEE.

• Yonsei Medical Journal
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• v.59 no.9
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• pp.1057-1063
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• 2018

Purpose: Coronary artery spasm (CAS) and diabetes mellitus (DM) are implicated in endothelial dysfunction, and insulin resistance (IR) is a major etiological cause of type 2 DM. However, the association between CAS and IR in non-diabetic individuals has not been elucidated. The aim of the present study was to evaluate the impact of IR on CAS in patients without DM. Materials and Methods: A total of 330 eligible patients without DM and coronary artery disease who underwent acetylcholine (Ach) provocation test were enrolled in this study. Inclusion criteria included both hemoglobin A1c <6.0% and fasting glucose level <110 mg/dL without type 2 DM. Patients were divided into quartile groups according the level of homeostasis model assessment of insulin resistance (HOMA-IR): 1Q (n=82; HOMA-IR<1.35), 2Q (n=82; $1.35{\leq}HOMA-IR<1.93$), 3Q (n=83; $1.93{\leq}HOMA-IR<2.73$), and 4Q (n=83; $HOMA-IR{\geq}2.73$). Results: In the present study, the higher HOMA-IR group (3Q and 4Q) was older and had higher body mass index, fasting blood glucose, serum insulin, hemoglobin A1c, total cholesterol, and triglyceride levels than the lower HOMA-IR group (1Q). Also, poor IR (3Q and 4Q) was considerably associated with frequent CAS. Compared with Q1, the hazard ratios for Q3 and Q4 were 3.55 (95% CI: 1.79-7.03, p<0.001) and 2.12 (95% CI: 1.07-4.21, p=0.031), respectively, after adjustment of baseline risk confounders. Also, diffuse spasm and accompanying chest pain during Ach test were more strongly associated with IR patients with CAS. Conclusion: HOMA-IR was significantly negatively correlated with reference diameter measured after nitroglycerin and significantly positively correlated with diffuse spasm and chest pain.

• Journal of Pharmacopuncture
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• v.25 no.3
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• pp.209-215
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• 2022

Objectives: Aqueous leaf extract of Tridax procumbens (ALETP) has potent relaxant activity. However, this relaxant activity in respiratory smooth muscle remains uninvestigated. This study investigates the effect of ALETP on the contractile activity of tracheal smooth muscle (TSM) in adult male Wistar rats. Methods: Twelve male Wistar rats divided into 2 groups and were treated with either 100 mg/kg of ALETP (ALETP treatment group) or vehicle (distilled water; control group) through oral gavage for 4 weeks. Dose responses of TSM from the 2 groups to acetylcholine (10^-9 to 10^-5 M), phenylephrine (10^-9 to 10^-5 M), and potassium chloride (KCl; 10^-9 to 10^-4 M) were determined cumulatively. Furthermore, cumulative dose responses to acetylcholine (10^-9 to 10^-5 M) after pre-incubation of TSM with atropine (10^-5 M), L-NAME (10^-4 M), indomethacin (10^-4 M), and nifedipine (10^-4 M), were determined. Results: Treatment with ALETP substantially inhibited TSM contraction stimulated by cumulative doses of acetylcholine, phenylephrine, and KCl. Furthermore, preincubation of TSM from the 2 groups in atropine significantly inhibited contractility in TSM. Incubation in L-NAME and indomethacin also significantly inhibited contractility in TSM of ALETP-treated rats compared to that of controls. Contractile activity of the TSM was also inhibited significantly with incubation in nifedipine in ALETP-treated rats. Conclusion: ALETP enhanced relaxant activity in rat TSM primarily by blocking the L-type calcium channel and promoting endothelial nitric oxide release. ALETP contains agents that may be useful in disorders of the respiratory tract.

• Current Research on Agriculture and Life Sciences
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• v.7
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• pp.231-235
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• 1989

The effects of choline and choline esters(acetylcholine, methacholine, carbachol, bethanechol) on motility of isolated rabbit jejunum segment were examined and $pD_2$ values of each drugs were compared. The results were as follows. In choline, there were revealed that maximum effective concentration was $10^{-2}M$, $ED_{50}$ was $2.4{\times}10^{-3}M$, and $pD_2$ value was 2.619. In acetylcholine, there were revealed that maximum effective concentration was $10^{-4}M$, effect was hardly showin in $10^{-9}M$ concentration, $ED_{50}$ was $0.5{\times}10^{-5}M$, and $pD_2$ value was 5.154. In methacholine, there were revealed that maximum effective concentration was $10^{-5}M$, effect was hardly shown in $10^{-9}M$ concentration, $ED_{50}$ was $9{\times}10^{-7}M$, and $pD_2$ value was 6.045. In carbachol, there were revealed that maximum effective concentration was $10^{-5}M$, effect was hardly shown in $10^{-11}M$ concentration, $ED_{50}$ was $5.7{\times}10^{-7}M$, and $pD_2$ value was 6.244. In bethanechol, there were revealed that maximum effective concentration was $10^{-4}M$, effect was hardly shown in $10^{-8}M$ concentration, $ED_{50}$ was $3.3{\times}10^{-6}M$, and $pD_2$ value was 5.480. Choline and choline esters caused contraction on motility of isolated rabbit jejunum segment. The order of $pD_2$ values of drugs was carbachol, methacholine, bethanechol, acetylcholine and choline (in the descending order of potency).

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.273-289
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• 1994

Reversible brain ischemia was produced by occluding both common carotid arteries for 5 min, and the effects of aminoguanidine (AG), $DL-{\alpha}-difluoromethylornithine$ (DFMO), MK-801, and nimodipine (NM) on the ischemia induced changes of the polyamine, glutamate and acetylcholine levels in the hippocampus CA1 subfield and the specific $[^3H]\;MK-801$ binding to the hippocampus synaptosomal membranes were studied with a histological reference of the cresyl violet stained hippocampus. The basal putrescine level $(PT:\;74.4{\pm}8.8\;nM)$ showed a rapid increase (up to 1.7 fold) for 5 min of ischemia, remained significantly increased for 6 h, and then resumed the further increase to amount gradually up to about 3 fold 96 h after recirculation. However, the level of spermidine was little changed, and the spermine level showed a transient increase during ischemia followed by a sustained decrease to about 40% of the preischemic level after recirculation. The increase of PT level induced by brain ischemia was enhanced with AG or MK-801, but it was reduced by DFMO or NM. The basal glutamate level $(GT:\;0.90{\pm}0.l4\;{\mu}M)$ rapidly increased to a peak level of $8.19{\pm}1.14\;{\mu}M$ within 5 min after onset of the ischemia and then decreased to the preischemic level in about 25 min after recirculation. And NM reduced the ischemia induced increase of GT level by about 25%, but AG, DFMO and MK-801 did not affect the GT increase. The basal acetylcholine level $(ACh:\;118.0{\pm}10.5\;{\mu}M)$ did little change during/after brain ischemia and was little affected by AG or NM. But DFMO and MK-801, respectively, produced the moderate decrease of ACh level. The specific $[^3H]\;MK-801$ binding to the hippocampus synaptosomal membrane was little affected by brain ischemia for 5 min. The control value (78.9 fmole/mg protein) was moderately decreased by AG and MK-801, respectively but was little changed by DFMO or NM. The microscopic findings of the brains extirpated on day 7 after ischemia showed severe neuronal damage of the hippocampus, particularly CA1 subfield. NM and AG moderately attenuated the delayed neuronal damage, and DFMO, on the contrary, aggravated the ischemia induced damage. However, MK-801 did not protect the hippocampus from ischemic damage. These results suggest that unlike to the mode of anti-ischemic action of NM, AG might protect the hippocampus from ischemic injury as being negatively regulatory on the N-methyl-D-aspartate (NMDA) receptor function in the hippocampus.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.13-20
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• 1991

There are some rather conflicting reports correlating ECS-induced changes of brain acetylcholine, and recently, Zawia and Bondy(1990) proposed the biological role of polyamine system in the long-term adaptive responses of brain to electrical stimulation. This study was undertaken to evaluate the effects of a single or repeated ECS(10mA, 100cps, 1sec; 5 ECS spread out over 9 days) on the brain acetylcholine(ACh) and polyamine contents of male mice. The ACh contents of temporal cortex(TCx) and decorticated cerebrum(dc-CB) were markedly increased by 79.9% and 49.4%, respectively, 10 and 30 min after ECS, and the increases were significantly attenuated with repeated 5 ECS, particularly in dc-CB. The putrescine concentrations of both TCx and dc-CB were little different and not affected by 1 ECS or 5 ECS. But the spermidine(Sd) concentration was higher in dc-CB and spermine(Sm) higher in TCx. While they were moderately decreased after 1 ECS, and their decreases were accentuated after 5 ECS, particularly in dc-CB.Sm(30mg/kg, i.p. inject. 30min before ECS) did not affect the ECS-induced increase of ACh content. Thease results suggest that both of brain ACh and polyamine may be implicated with the long-term adaptive responses to electrical stimulation

• Journal of Embryo Transfer
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• v.20 no.3
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• pp.191-200
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• 2005

Many studies have shown that the development of mouse early 2-cell embryos in vitro is related with the intracellular $Ca^{2+}$ changes. In ICR strain mouse, the development of embryos arrests at early 2-cell stage, but the arrested early 2-cell embryos can be rescued by the addition of $Ca^{2+}$-related materials. Acetylcholine (ACh) increases intracellular $Ca^{2+}$ concentration ([$Ca^{2+}$]i) via the mAChR-PLC-IP3 pathway in mouse oocytes. We examined whether ACh rescues 2-cell block in mouse. In early 2-cell embryos, ACh increased [$Ca^{2+}$]i in a dose-dependent manner (p<0.001), and had an effect on rescue of 2-cell block and embryonic development. To identify the signal pathway involved in ACh-induced rescue of 2-cell block, we first applied an agonist of ACh receptor (AChR). Like ACh, carbachol increased intracellular $Ca^{2+}$ concentration ([$Ca^{2+}$]i) and atropine, an antagonist of ACh receptor, blocked the ACh-induced $Ca^{2+}$ increase. In $Ca^{2+}$-free medium, ACh also increased [$Ca^{2+}$]i, indicating that $Ca^{2+}$ increased by ACh is mainly released from the intracellular $Ca^{2+}$ store. The ACh-induced $Ca^{2+}$ increase was blocked by PLC inhibitor (U73122), ryanodine receptor (RyR) antagonist (dantrolene), and CaM KII inhibitor (KN-93), but not by IP3R antagonists (xestospongin C). These results show that ACh increases intracellular $Ca^{2+}$ concentration via mAChR/PLC/RyR, and this contributes to the rescue of 2-cell block.

• Journal of Sasang Constitutional Medicine
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• v.9 no.2
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• pp.227-243
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• 1997

The experimental study used in this paper was done to examine the clinical effects of Taeumchowetang for the gastric ulcer and the function of gastrointestinal tract using rats and mice which were administered orally the water extraction from Taeumchowetang. Then, the counter-action of the water extraction on the isolated ileum and gastric fundus, the inhibitory effects of pylorus-ligated ulcer and indomethacin-induced ulcer, the associations with gastric juice secretion, total acidity, pepsin output, the transportability in the small and large intestine, were studied with administering acetylcholine chloride and barium chloride. In addition, it was investigated whether the central nervous system related to pain control and sleeping time was influenced by Taeumchowetang. The following results have been obtained; 1. As resulting from injection of acetylcholine chloride and barium chloride into the isolated ileum of rats and mice, Taeumchowetang led to have an inhibitory effect on the muscle contraction of the ileum. Then, acetylcholine chloride was measured as lower effect than barium chloride 2. For the inhibitory effect on contraction for the gastric fundus strip in rats by either acetylcholine chloride or barium chloride, the one showed low inhibitory effect, on the other hand the other showed density-dependent effect. 3. The water extraction was given on the pylorus ligated ulcer with using two different administration groups of 1,300mg/kg and 2,600mg/kg, each result was measured as 22.9% and 36.5% for an ulcerous inhibitory effect (p<0.05). 4. According to the two administration groups, the preventive effect was tabulated 18.1% and 29.3% for indomethacin-induced ulcer (p<0.05, P<0.01). 5. For associations with gastric juice secretion, total acidity, pepsin output in the administration group 2,600mg/kg, Taeumchowetang was recognized as having an inhibitory effects related to suppressive actions involving gastric juice secretion(p<0.05), and free acidity(p<0.01), but there was no significant association with total acidity and pepsin output. 6. To know the transportability in the intestine, BaSO4 solution was used. The transportability of the small intestine in the administration group 2,600mg/kg was 22.2% which was statistically significant compared with the large intestine's transportability(P<0.01). 7. In the administration group 1,300mg/kg and 2,600mg/kg, analgesic effect with against acetic acid was measured as being 16.8% and 24.4% which was shown as statistically siginificant(p<0.01). 8. No statistically significant association between Taeumchowetang and sleeping time was found in both 1,300mg/kg and 2,600mg/kg by administering phenobarbital-Na. According to the results of this study, Taeumchowetang has agreed with the effects of literature review. Further more in this study, Taeumchowetang also has preventive effects on pylorus-ligated ulcer. Hence, Teaumchowetang can be significant effect such as both anti ulcer agent and increasing gastric activity for the patients who suffer from gastric ulcer.

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