• Journal of Chest Surgery
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• v.27 no.1
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• pp.9-14
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• 1994

Substance P[SP] has been known to be a peptide which may be plays a role as a neurotransmitter in central nervous system as well as peripheral autonomic nervous system. It has been reported that SP was widely distributed in the nerve of the tracheal smooth muscle and induced the muscle contraction. However, definite action mechanism of SP in the tracheal smooth muscle was not clear, yet. Thus, present experiment was performed to elucidate an effect of substance P and an action mechanism on contraction of the smooth muscle in rabbits. In order to find a neural mechanism to the effect of SP on the tracheal smooth muscle contraction, atropine sulfate, tetrodotoxin, propranol and phentolamine were administered at 10 min before the addition of SP. Otherwise,to find effect of SP antagonists on the action of SP, [D-Pro2, D-Try7,9]SP, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP and [D-Pro4, D-Trp7,9]SP were administered as a same fashion. These following results were obtained. 1] SP induced contraction of the tracheal smooth muscle under resting condition and the contraction was increased dose-dependently. 2] Cholinergic blocker[atropine], neural blocker[tetrodotoxin] and adrenergic blocker[propranol and phentolamine] didn`t have an effect on the contractile response. 3] Three SP antagonists inhibited the contractile response. 4] Isoproterenol relaxed the contraction induced by SP. The above results suggested that SP induced contraction of the tracheal smooth muscle directly act to the smooth muscle in rabbits. The autonomic nervous system did not seem to participate in the SP action.

• YAKHAK HOEJI
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• v.50 no.3
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• pp.208-213
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• 2006

Rat aortic ring preparations were mounted in organ baths, exposed to sodium cyanide $(0.01{\sim}1.0\;mM)$ for 10 min, and then subjected to contractile agents or relaxants such as acetylcholine, sodium nitroprusside and isoproterenol. Presence of low concentration of sodium cyanide did not affect the contractile response to KCl or phenylephrine in the aortic rings with intact endothelium or endothelium denuded. Sodium nitroprusside but not acetylcholine or isoproterenol augmented phenylephrine-induced intact or denuded vascular contraction in the presence of low concentration of sodium cyanide. In conclusion, this study provides the evidence concerning the potentiating effect of sodium nitroprusside on the contraction induced by phenylephrine in rat aortic rings regardless of endothelial function.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.299-305
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• 1997

In order to investigate the pharmacological properties of ι-muscone, effects of ι-muscone and musk were studied on the cardiovascular system with various experimental models. In isolated rat aorta, ι-muscone and musk made the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) in endothelium-containing rings of the rat aorta, but not in endothelium-denuded rings. However, ι-muscone and musk in the presence of the inhibitor of NO synthase and guanylate cyclase did not make the relaxation of blood vessels. In spontaneously hypertensive rats (SHRs), ι-muscone and musk slightly reduced blood pressure but significantly decreased heart rate. In the isolated perfused rat hearts, ι-muscone and musk did not affect significantly on LVDP, contractile force, coronary flow and (-dp/dt)/(+dp/dt). These results suggest that ι-muscone and musk have weak cardiovascular effects with relaxation of blood vessel and decrease of heart rate, but without significant cardiac functions.

• Journal of Nutrition and Health
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• v.30 no.3
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• pp.244-251
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• 1997

The effects of Artemisia princeps var orientalis(mugwort), Circium japonicum var ussuriense (Unggungqui) on cadiovascular system in hyperlipidemic rats were investgated. Thirty rats devided into 5 experimental groups, were fed with the diet contained 1% chlesterol, 0.25% sodium cholate, 10% coconut oil and 5% lard by the same method of previous paper1). Contractile and relaxation responses in the isolated artria and thoracic aortae were measured and the morphological changes of the aortic endotherium from the rats were inspected. The responses of the right atrial to isoproterenol were significantly lower value in Ungungqui powder diet group(UP) and mugwort powder diet group(MP) than the control. The contraction force by injectin of phenylephrine and calcium in isolated thoracic aortae was significantly low value in the UP and the MP groups compaired to the control. The relaxation rate by acetylcholine in isolated thoracic aortae represented significantly higher value in UP than control. The morphological changes of endothelial cell suface was smallest in UP and the damage of endothelium by retarded in MP. Although Ungungqui and mugwort extract diet groups(UE, ME) were advanced, those were less than control.

• YAKHAK HOEJI
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• v.58 no.1
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• pp.16-20
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• 2014

KR-31064 was developed for the strong angiotensin II receptor antagonist among the one of pyridyl imidazol series compounds. To investigate the receptor-ligand binding characteristics of this nonpeptide antagonist, binding experiments were deployed in various conditions and ex vivo contractile responses were tested toward the standard compound, losartan. Receptor binding experiments with radiolabeled angiotensin II, the $IC_{50}$ value for KR-31064 resulted 0.67 nM without any activities toward type 2 angiotensin II receptor. The comparative potency against losartan was more than 18 fold and the specific activity in type 1 angiotensin II receptor was more than 10,000 fold comparing to the type 2 receptor. Scatchard analysis of saturation binding data showed KR-31064 acted on the receptor in a competitive mode. KR-31064 inhibited the contractile response derived by angiotensin II ($pK_B$: 9.86) similar to that of losartan with decreased maximum signals. As a potent and specific type 1 angiotensin II receptor antagonist, KR-31064 may have possibilities for the development of diagnostic ligands that can be used as tools for various biochemical research experiments and non-invasive diagnostics.

• Korean Journal of Veterinary Research
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• v.36 no.4
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• pp.821-828
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• 1996

To elucidate the neuromodulation of neuropeptide Y and $\alpha,\;\beta$-methylene ATP on the neurogenic contraction of electrical perivascular nerve stimulation and the contractile response of noradrenaline from polygraph in the isolated renal artery of rabbit. 1. The neurogenic contraction induced by perivascular nerve stimulation was the voltage-dependent manner(10-100V) in the isolated renal artery of rabbit. 2. Neuropeptide Y(0.1uM) and $\alpha,\;\beta$-methylene ATP(1uM) increased the contractile responses of noradrenaline in the isolated renal artery of rabbit. 3. Neuropeptide Y(0.1uM) and $\alpha,\;\beta$-methylene ATP(1uM) increased the neurogenic contraction of electrical perivascular nerve stimulation in the isolated renal artery of rabbit. These results suggest that neuropeptide Y and $\alpha,\;\beta$-methylene ATP neuromodulated on the neurogenic contraction of electrical perivascular nerve stimulation on the isolated renal artery of rabbit.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.381-388
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• 1996

The hemodynamic changes in septic patients produced by inhalational anesthetics are sufficient to threaten the anesthesiologists. The effect of hydroxocobalamin, a vitamin $B_{12a}$, on contractile responses to phenylephrine during administration of inhalational anesthetics were evaluated in aortic ring preparations obtained from LPS-treated rats. The sepsis was developed by intraperitoneal injection of LPS (1.5 mg/kg for l8h) and confirmed by iNOS expression using RT-PCR. Statistical significances (P<0.05) were analyzed by Student's t-test or paired t-test according to data characteristics. The blood pressure, but not heart rate, was decreased in LPS-treated rats as compared to control rats. The contractile response to phenylephrine were dose-dependently increased from the doses of $10^{-8}\;M$ to that of $10^{-5}$ and were attenuated in LPS-treated rings. Both halothane and enflurane, at the doses of 1 MAC, decreased the contractile responses to phenylephrine while isoflurane did not significantly affect the contractile responses. Hydroxocobalamin ($10^{-5}$ M) significantly potentiated the contractile responses in the LPS-treated aortic ring preparations during administration of each inhalational anesthetic or not. From these results, it is suggested that hydroxocobalamin may improve the hemodynamics of septic patients during inhalational anesthesia. Abbreviations: LPS, lipopolysaccharide; RT-PCR, reverse transcription-polymerase chain reaction; MAC, minimum alveolar concentration; iNOS, inducible nitric oxide synthase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.65-72
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• 1993

Ultraviolet light radiation (UVR) did not affect resting tension of isolated thoracic aortae of rats. In aortic rings contracted with phenylephrine, however, UVR produced contractile and relaxant responses in preparations with and without endothelium, respectively. The contractile response was dependent upon the duration $(10{\sim}320\;sec)$ of irradiation, while the relaxation was not. UVR-induced contractions in endothelium-intact rings were significantly potentiated by increasing the concentrations of phenylephrine from $10^{-7}M$ to $10^{-5}M$, and also by addition of $10^{-6}M$ acetylcholine, $10^{-7}M$ isoproterenol and $3.5{\times}10^{-8}M$ nitroglycerine. However, addition of $10^{-6}M$ phentolamine, or $10^{-7}M$ to $10^{-6}M$ LY83583 inhibited the contraction or reversed the contraction to a relaxation. In endothelium-removed preparations the UVR-induced relaxation was attenuated by increasing concentractions of phenylephrine, and by addition of isoproterenol, nitroglycerin, phentolamine or LY83583. These results suggest that UVR produces contractile and relaxant responses in rat thoracic aortae with and without endothelium, respectively, and that the contractile effect results from the inhibition of endothelium-derived relaxing factor (EDRF) release by UVR the inhibition of and/or is in part re-lated to some endothelium-derived contractile factors (EDCFs).

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.23-30
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• 1981

1) Effects of McN-A-343, clonidine and cocaine on the contractile response of the rat and rabbit vas deferens to field stimulation were investigated. The action mechanisms of these drugs have shown to be associated with endogenous norepinephrine(NE). 2) The contractile response to the stimulation of 5-10 Hz was markedly inhibited by the cumulative doses of McN-A-343 (0.003, 0.03, $0.3{\mu}g/ml$), clonidine (0.003, $0.3{\mu}g/ml$) and cocaine $(0.03\;{\mu}g/ml)$. The inhibition was antagonized by yohimbine and pjperoxan. 3) The inhibitory effect of McN-A-343 $(0.03{\mu}g/ml)$ and cocaine $(0.03{\mu}g/ml)$ was markedly enhanced by the same dose of cocaine and McN-A-343, respectively. This enhanced inhibition was also antagonized by yohimbine. 4) The contractile response to the stimulation of 0.01 Hz and 5-10 Hz was markedly potentiated by comparatively large doses of McN-A-343 $(30\;{\mu}g/ml)$ and $(3\;{\mu}g/ml)$. This potentiation was not observed in the presence of thymoxamine. The potentiation by McN-A-343 also did not appear in the presence of atropine. 5) The contractile response to the above stimulation was potentiated by muscarine and the potentiation was markedly attenuated in the presence of thymoxamine and atropine.

• The Korean Journal of Physiology
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• v.18 no.2
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• pp.151-162
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• 1984

The mechanism of the contractile response of longitudial muscle of rabbit ileum to substance P (SP) has been investigated. The contractions in rabbit ileum under various conditions were recorded isometrically The following results were obtained. 1) The contractions by SP increased according to concentrations. SP·induced contraction was not sustained but faded rapidly at $10^{-7}M$. The response to the commutative addition of SP was decreased in comparison to the response to separate administration of each concentration . 2) The response to $10^{-8}M$ SP after 5 min application cf $10^{-7}M$ SP was increased with increasing the time interval between the administration of $10^{-7}$ and $10^{-8}M$ SP. 3) The treatment of rabbit ileum by $10^{-7}M$ SP for 5 min didn't decrease the response to $10^{-6}M$ acetylcholine. 4) $10^{-6}M$ atropine had no effect of the contractile response to $10^{-7}M$ SP. The response to $10^{-7}M$ SP was normal or subnormal in the presence of 3 mM tetraethylammonium(TEA). 5) 100k solution, $10^{-4}M$ ouabain, and Na-free solution inhibited the response to $10^{-8}M$ SP and 3 mM TEA completely, and to $10^{-7}M$ SP incompletely. 3 mM TEA induced a considerable contraction in K-free solution, but $10^{-8}M$ SP didn't induce the contraction. $10^{-6}M$ norepinephrine decreased the contractile responses to SP and TEA. 6) The contractile response to $10^{-7}M$ SP was dependent on the extracellular $Ca^{2+}$ concentrations to 1.8 mM. 7) The contractile response to $10^{-7}M$ SP remained 15% of the maximal response after bathing the ileum in a Ca-free solution for 2.5 min. 8) The responsiveness to SP was completely lost within 10 min of bathing in Ca-free solution, but was restored by the exposure to $Ca^{2+}$. The restorative effect of $Ca^{2+}$ depended on the concentration of $Ca^{2+}$, and on time for which the tissue exposed to this $Ca^{2+}$ concentration. These results suggest that there are two mechanisms of the action by which the low concentrations of substance P causes the contraction of intestinal smooth muscle: the reduction of K conductance and a mechanism dependent on the extracellular $Ca^{2+}$, and that high concentration of SP may elicit a contraction by releasing $Ca^{2+}$ from an intracellular store, which is not as sensitive to removal of extracellular $Ca^{2+}$ or as easily accessible to EGTA as the extracellular space of the muscle. The location of this store is not known; it may be associated with the internal side of the cell membrane.