• YAKHAK HOEJI
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• v.41 no.6
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• pp.829-836
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• 1997

Studies on the effect of quinones on cardiac function has been conducted with normal hearts. But not with injured hearts, I.e. ischemia/reperfusion-injured heart. Quinone compounds are known to produce oxygen free radicals during metabolism, and for this reason, quinones are implicated in the aggravation of ischemia/reperfusion injury or cardioprotection, as in the case of ischemic preconditioning depending on the experimental conditions. The present study was carried out to examine the effect of 2-chloro-3-(4-cyanophenylamino)-1.4-naphthoquinone (NQ-Y15) on cardiac function of ischemic/reperfused and normal rat hearts. In isolated perfused hearts, various functional parameters such as left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (EDP) and maximum positive and negative dP/dt ($[\pm}dP/dt_{max}$), time to contracture, heart rate (HR) and coronary flow rate (CFR) were measured before and 30 min after dosing and following 25 min ischemia/30min reperfusion. NQ-Y15 increased LVDP, +dP/$d_{max}$and -dP/$dt_{min}$ by 18%. 30%, and 40%, respectively. There were no significant changes in other haemodynamic parameters. After ischemia/reperfusion injury, pretreatment with NQ-Y15 induced a significant decrease in LVDP and $[\pm}dP/dt_{max}$, but an increase in EDP. LDH-release was not significantly increased. These results suggested that NQ-Y15 may augment the ventricular contractility but it makes hearts more vulnerable to ischemia/reperfusion injury.

• The Korean Journal of Physiology
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• v.11 no.2
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• pp.33-39
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• 1977

It has been reported that administration of Ginseng powder to the Guinea pig reduces anaphylactic shook induced by horse serum (Lee, 1939). However, Lee et al. (1960) and Paik et al. (1976) have demonstrated that Ginseng increases capillary permeabilites and histamine release from the mast cell. These facts suggest that Ginseng acts directly on the bronchial muscle causing it to dilate. Recently, a number of investigators(Kidakawa & Iwasiro 1963; Takagi et al. 1973) have reported that Ginseng reverses acetylcholine- or histamine- induced contraction in the isolated Guinea pig ileum. We, therefore, undertook the present study to examine if Ginseng relaxes the spasm of bronchial muscle induced by acetylcholine or histamine. We have also attempted to identify the mechanism of the Ginseng effect. Male Guinea Pig was sacrificed by a blow on the head, The trachea was removed and sectioned with scissors into about 12 rings. After the 'C' shaped ring of cartilage was sectioned the one end of ring was tied to the bottom of the incubation bath and the other end was connected to a force transducer (FTO 3C) to record tension on a Polygraph. When the antispasmodic action of Ginseng effect was first examined in the normal trachea which was not treated by the drug. And then the Ginseng effect was tested in the muscle treated by histamine hydrochloride, acetylcholine hydrochloride or barium chloride. The results indicate that Ginseng alcohol extract relaxes the contraction of isolated tracheal muscle induced by histamine $(1{\mu}g/ml{\sim}10{\mu}g/ml)$, acetylcholine $(1{\mu}g/ml{\sim}5{\mu}g/ml)$ and barium chloride (1.5 mg/ml). The mechanism of this action is in Pa.1 due to nonspecific antimuscarinic and antihistaminic effect and in part by predominant action in the adrenergic ${\beta}-receptor$ although the ${\alpha}-receptor$ is also involved. We, therefore, conclude that Ginseng can be act as a bronchodilator.

• Journal of Microbiology and Biotechnology
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• v.25 no.8
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• pp.1371-1379
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• 2015

The Ca_v1.2 Ca²⁺ channel is essential for cardiac and smooth muscle contractility and many physiological functions. We mutated single, double, and quadruple sites of the four potential Asn (N)-glycosylation sites in the rabbit Ca_v1.2 into Gln (Q) to explore the effects of Nglycosylation. When a single mutant (N124Q, N299Q, N1359Q, or N1410Q) or Ca_v1.2/WT was expressed in Xenopus oocytes, the biophysical properties of single mutants were not significantly different from Ca_v1.2/WT. In comparison, the double mutant N124,299Q showed a positive shift in voltage-dependent gating. Furthermore, the quadruple mutant (QM; N124,299,1359,1410Q) showed a positive shift in voltage-dependent gating as well as a reduction of current. We tagged EGFP to the QM, double mutants, and Ca_v1.2/WT to chase the mechanisms underlying the reduced currents of QM. The surface fluorescence intensity of QM was weaker than that of Ca_v1.2/WT, suggesting that the reduced current of QM arises from its lower surface expression than Ca_v1.2/WT. Tunicamycin treatment of oocytes expressing Ca_v1.2/WT mimicked the effects of the quadruple mutations. These findings suggest that Nglycosylation contributes to the surface expression and voltage-dependent gating of Ca_v1.2.

• The Korean Journal of Pharmacology
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• v.13 no.1 s.21
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• pp.7-12
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• 1977

Recently several reports have claimed that the bath temperature changes, such as lower bath temperature, produce supersensitivity on the positive chronotropic effect of catecholamine in cat, mouse and guinea pig atria. However, others showed controversial results against temperature-dependent supersensitivity. Similarly, the inotropic effect of ouabain is diminished in febrile state, however some investigators indicated that cardiac glycoside showed less toxicities and less effects in hypothermic condition. In this study, the effects of norepinephrine and epinephrine on inotropy and chronotropy in isolated rat atria was investigated by changing the temperature of bath ($30^{\circ}C$, $^35{\circ}C$ and $38^{\circ}C$). In addition, the effects of ouabain on atria in hypothermic bath was also studied. The followings are the results. 1. At the lower bath temperature isolated rat atrial rate was decreased and contractility was increased. 2. The chronotropic responses to norepinephrine and epinephrine in $38^{\circ}C$ were decreased when the bath temperature lowered to $35^{\circ}C$ or $30^{\circ}C$, while the inotropic responses were not affected. 3. Hypothermic supersensitivity to norepinephrine or epinephrine was not observed in rat atrium. 4. The inotropic response to ouabain was potentiated but chronotropic response was diminished by a lowering in the bath temperature. In conclusion, the chronotropic response of rat atrium to catecholamine was decreased, however, hypothermic supersensitivity was no longer present in rat atrium and the inotropic response of ouabain was increased at lower bath temperature.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.1
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• pp.55-61
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• 2000

The present study was conducted to investigate the possible role of the sympathetic nervous system in two-kidney, one clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt hypertension. 2K1C and DOCA- salt hypertension were made in Sprague-Dawley rats. Four weeks after induction of hypertension, systolic blood pressure measured in conscious state was significantly higher in 2K1C $(216{\pm}18\;mmHg)$ and DOCA-salt $(205{\pm}29\;mmHg)$ groups than that in control $(128{\pm}4\;mmHg).$ The third branches (＜300 ${\mu}m$ in outer diameter) of the mesenteric artery were isolated and cut into ring segments of $2{\sim}3$ mm in length. Each ring segment was mounted in tissue bath and connected to a force displacement transducer for measurement of isometric tension. The arterial rings were contracted by application of norepinephrine (NE) in a dose-dependent manner. The amplitude of the NE-induced contraction of the vessels was significantly larger in hypertension than in control. The NE-induced contraction was significantly enhanced by neuropeptide Y (NPY) in hypertension. Reciprocally, NPY-elicited vasocontraction was increased by NE in hypertension. These results suggest that the sympathetic nervous system contributes to the development of 2K1C and DOCA-salt hypertension.

• The Journal of Korean Physical Therapy
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• v.19 no.4
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• pp.1-14
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• 2007

Background: It is generally accepted that skeletal muscle contraction is triggered by nerve impulse and intracellular $Ca^{2+}\;([Ca^{2+}]_i)$ released from intracellular $Ca^{2+}$ stores such as sarcoplasmic reticulum (SR). Specifically, this process, called excitation-contraction (E-C) coupling, takes place at intracellular junctions between the plasma membrane, the transverse (T) tubule L-type $Ca^{2+}$ channel (dihydropyridine-sensitive L-rype $Ca^{2+}$ channel, DHPR, also called tetrads), and the SR $Ca^{2+}$ release channel (ryanodine-sensitive $Ca^{2+}$ release channel, RyR, also called feet) of internal $Ca^{2+}$ stores in skeletal muscle cells. Furthermore, it has been reported that the $Ca^{2+-}$ dependent and -independent contraction determine the expression of skeletal muscle genes, thus providing a mechanism for tightly coupling the extent of muscle contraction to regulation of muscle plasticity-related excitation-transcription (E-T) coupling. Purpose: Expression and activity of plasticity-associated enzymes in gastrocnemius muscle strips have not been well studied, however. Methods: Therefore, in this study the expression and phosphorylation of E-C and E-T coupling-related mediators such as protein kinases, ROS(reactive oxygen species)- and apoptosis-related substances, and others in gastrocnemius muscles from rats was examined. Results: I found that expression and activity of MAPKs (mitogen-activated protein kinases, ERK1/2, p38MAPK, and SAPK/JNK), apoptotic proteins (cleaved caspase-3, cytochrome c, Ref-1, Bad), small GTP-binding proteins (RhoA and Cdc42), actin-binding protein (cofilin), PKC (protein kinase C) and $Ca^{2+}$ channel (transient receptor potential channel 6, TRPC6) was observed in rat gastrocnemius muscle strips. Conclusion: These results suggest that MAPKs, ROS- and apoptosis-related enzymes, cytoskeleton-regulated proteins, and $Ca^{2+}$ channel may in part functionally import in E-C and E-T coupling from rat skeletal muscles.

• Toxicological Research
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• v.12 no.2
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• pp.195-201
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• 1996

Endotoxic shock causes death in humans and animals via extreme hypoperfusion of peripheral organs. A massive production of nitric oxide (NO) both from the endothelical cells and smooth muscle cells has been proposed as a possible mechanism in this process. Since NO attenuated the contractility to vasoconstricting agents such as norepinephrine (NE) by directly acting on the smooth muscle cells, this mechanism was considered mainly as a postsynaptic mechanism. In this research it was investigated whether NO, thus released, also participates in the presynaptic events for the regulation of vascular tone in endotoxic shock. The role of NO was studied by adding NO donors or NO synthase inhibitor $N^\omega $methyl-L-arginine (NMA) in stimulated sympathetic nerves of the mesenteric vascular bed and the Langendorff heart of rats. Sodium nitroprusside (SNP), an NO donor, reduced the pressor responses of isolated mesenteric artery either to electrical stimulation or exogenously administered phenylephrine (PE). In this mesentery, although neither agent influenced NE release, in the presence of the adrenergic $\alpha_2$-receptor antagonist yohimbine, elecrical stimulation-evoked NE release was augumented by SNP. In the heart SNP facilitated the NE release induced by electrical stimulation, while NMA had no effect. From these results it is proposed that there exists a local reflex phenomenon in the junction between the sympathetic nerve terminals and the smooth muscle of resistance blood vessels; by which sympathetic responses are reduced by NO at the postjunctional level while NO facilitates NE release contributing to augumentation of sympathetic tone. All these facts suggest that NO produced during endotoxic shock has dual effects: whereas NO blunts the vasoconstrictive activity of NE at the postsynaptic level, NO presynaptically facilitates the release of NE from sympathetic nerve terminals.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.643-655
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• 2018

Background/Aims Irritable bowel syndrome (IBS) is a common disease characterized by intestinal dysmotility, the mechanism of which remains elusive. We aim to determine whether the high-affinity choline transporter 1 (CHT1), a determinant of cholinergic signaling capacity, modulates intestinal motility associated with stress-induced IBS. Methods A rat IBS model was established using chronic water avoidance stress (WAS). Colonic pathological alterations were evaluated histologically and intestinal motility was assessed by intestinal transit time and fecal water content (FWC). Visceral sensitivity was determined by visceromotor response to colorectal distension. RT-PCR, western blotting, and immunostaining were performed to identify colonic CHT1 expression. Contractility of colonic muscle strips was measured using isometric transducers. enzyme-linked immunosorbent assay was used to measure acetylcholine (ACh). We examined the effects of MKC-231, a choline uptake enhancer, on colonic motility. Results After 10 days of WAS, intestinal transit time was decreased and fecal water content increased. Visceromotor response magnitude in WAS rats in response to colorectal distension was significantly enhanced. Protein and mRNA CHT1 levels in the colon were markedly elevated after WAS. The density of CHT1-positive intramuscular interstitial cells of Cajal and myenteric plexus neurons in WAS rats was higher than in controls. Ammonium pyrrolidine dithiocarbamate partly reversed CHT1 upregulation and alleviated colonic hypermotility in WAS rats. Pharmacological enhancement of CHT1 activity by MKC-231 enhanced colonic motility in control rats via upregulation of CHT1 and elevation of ACh production. Conclusion Upregulation of CHT1 in intramuscular interstitial cells of Cajal and myenteric plexus neurons is implicated in chronic stress-induced colonic hypermotility by modulation of ACh synthesis via nuclear factor-kappa B signaling.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.393-402
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• 2019

Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with $IC_{50}$ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect $I_{Na}$, $I_{Ks}$ or $I_{K1}$, but decreased $I_{hERG}$ in a dose-dependent manner ($IC_{50}$: $6.53{\mu}M$). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to $3{\mu}M$, but it at $10{\mu}M$ induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.1
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• pp.11-18
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• 2022

Background: The vasoconstrictive effect of epinephrine in local anesthetics affects the heart, which leads to hesitation among dentists in injecting local anesthetics into patients with cardiovascular disease. Due to its vasoconstrictive effects, the present study investigated the effects of vasopressin administration on cardiac function in rats. Methods: Experiment 1 aimed to determine the vasopressin concentration that could affect cardiac function. An arterial catheter was inserted into the male Wistar rats. Next, 0.03, 0.3, and 3.0 U/mL arginine vasopressin (AVP) (0.03V, 0.3V, and 3.0V) was injected into the tongue, and the blood pressure was measured. The control group received normal saline only. In Experiment 2, following anesthesia infiltration, a pressure-volume catheter was placed in the left ventricle. Baseline values of end-systolic elastance, end-diastolic volume, end-systolic pressure, stroke work, stroke volume, and end-systolic elastance were recorded. Next, normal saline and 3.0V AVP were injected into the tongue to measure their effect on hemodynamic and cardiac function. Results: After 3.0V administration, systolic blood pressures at 10 and 15 min were higher than those of the control group; they increased at 10 min compared with those at baseline. The diastolic blood pressures at 5-15 min were higher than those of the control group; they increased at 5 and 10 min compared with those at baseline. The preload decreased at 5 and 10 min compared to that at baseline. However, the afterload increased from 5 to 15 min compared with that of the control group; it increased at 10 min compared with that at baseline. Stroke volume decreased at 10 and 15 min compared with that of the control group; it decreased from 5 to 15 min compared with that at baseline. Stroke work decreased from 5 to 15 min compared with that of the control group; it decreased from 5 to 15 min compared with that at baseline. Conclusion: Our results showed that 3.0 U/mL concentration of vasopressin resulted in increased blood pressure, decreased stroke volume and stoke work, decreased preload and increased afterload, without any effect on myocardial contractility.