• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.77-86
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• 2022

The effect of PHAR-DBH-Me, a cannabinoid receptor agonist, on different cardiovascular responses in adult male rats was analyzed. The blood pressure was measured directly and indirectly. The coronary flow was measured by Langendorff preparation, and vasomotor responses induced by PHAR-DBH-Me in aortic rings precontracted with phenylephrine (PHEN) were analyzed. The intravenous injection of the compound PHAR-DBH-Me (0.018-185 ㎍/kg) resulted in decreased blood pressure; maximum effect was observed at the dose of 1,850 ㎍/kg. A concentrationdependent increase in the coronary flow was observed in a Langendorff preparation. In the aortic rings, with and without endothelium, pre-contracted with PHEN (10^-6 M), the addition of PHAR-DBH-Me to the superfusion solution (10^-12-10^-5 M), produced a vasodilator response, which depends on the concentration and presence of the endothelium. L-NAME inhibited these effects. Addition of CB₁ receptor antagonist (AM 251) did not modify the response, while CB₂ receptor antagonist (AM630) decreased the potency of relaxation elicited by PHAR-DBH-Me. Indomethacin shifted the curve concentration-response to the left and produced an increase in the magnitude of the maximum endothelium dependent response to this compound. The maximum effect of PHAR-DBH-Me was observed with the concentration of 10^-5 M. These results show that PHAR-DBH-Me has a concentration-dependent and endothelium-dependent vasodilator effect through CB₂ receptor. This vasodilation is probably mediated by the synthesis/release of NO. On the other hand, it is suggested that PHAR-DBH-Me also induces the release of a vasoconstrictor prostanoid.

• 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.

• 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.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.27-37
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• 1995

In anesthetized rats, we examined the possibility that endothelium-derived relaxing factor (EDRF) or nitric oxide (NO) released in response to cholinergic mechanism may contribute to the reflex autoregulation of cerebral blood flow. Suffusion with mock cerebrospinal fluid (CSF), containing acetylcholine (ACh, $10^{-9}{\sim}10^{-6}M$) evoked concentration-dependent vasodilatation of the resting pial artery (mean, $19.3{\pm}1.7{\mu}m$, n=36), which was significantly inhibited not only by $N{\omega}$-nitro-L-arginine (L-NNA, $10^{-5}M$) but also by methylene blue ($10^{-6}M$) and oxyhemoglobin ($10^{-6}M$). The muscarinic receptors in the endothelium of pial artery implicated in the release of EDRF were considered to be $M_1\;and\;M_3$ subtypes. When suffused with mock CSF containing L-arginine it caused a transient vasodilatation, which was strongly inhibited by LY 83583 ($10^{-5}M$), but not by L-NNA ($10^{-5}M$). Additionally, both ACh- and L-arginine-induced vasodilation were significantly inhibited by glibenclamide, a specific ATP-sensitive $K^+$ channel blocker. On the other hand, changes in pial arterial diameter were plotted as a function of changes in systemic arterial blood pressure. The slopes of regression lines for vasodilation and vasoconstriction were not affected by pretreatment with $10^{-5}M$ L-NNA, but significantly reduced by $3{\times}10^{-6}M$ glibenclamide. Thus it is suggested that the reflex vasodilation of rat pial arteries in response to a transient hypotension is not mediated by EDRF (NO).

• The Korean Journal of Pharmacology
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• v.31 no.3
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• pp.285-290
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• 1995

This study was undertaken to define the varying responses of vascular smooth muscle to different wavelengths of ultraviolet radiation and to relate them to the changes in cyclic GMP contents. The ring preparations of rat thoracic aorta with intact or removed endothelium were irradiated with the ultraviolet or visible light (UVR) of wavelengths in step of 10 nm between 250 and 500 nm from xenon lamp of a spectrofluorometer, and the changes in vascular tension were recorded. For cyclic GMP assay, the preparations, pretreated with phenylephrine as in the tension experinents, were frozen after irradiation and homogenated in trichloroacetic acid. The supernatant was extracted with ether and the cyclic GMP contents were measured with radioimmunoassay. In the endothelium-intact preparations, biphasic responses, vasoconstriction (UVR-contraction) followed by vasodilatation (UVR-dilatation), were observed. The maximal UVR-contraction was observed at 320 nm, while the maximal vasodilatation was elicited at 420 nm. In the endothelium-removed rings, however, only vasodilatation was observed, with the maximal vasodilatation taking place at 370 nm. The cyclic GMP contents were not affected by the Irradiation with 320 nm for 30 sec or 1 min in the endothelium-intact preparations, while it was significantly increased by 380 and 420 nm. In the endothelium-removed preparations, UVR of 370 nm markedly increased the cyclic GMP contents. The present study indicates that the increase in cyclic GMP is closely related to vasodilatation induced by UVR of 420 nm in the endothelium-intact or 370 nm in the denuded preparations, whereas it is not involved in the vasoconstriction induced by UVR of 320 nm in the intact rings, and the mechanism leading to UVR-contraction remains to be clarified. These observations suggest that nitric oxide-cyclic GMP system is closely related to the UVR-dilatation in rat aortic preparation, while it is not involved in the UVR contraction.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.203-212
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• 1993

This study was designed to observe hypoxia-induced mechanical responses of porcine cerebral artery and to clarify their possible mechanisms. Hypoxia produced a transient vasoconstriction, recovering to the basal tension within 10 min and subsequent reoxygenation produced a biphasic (relaxalion-contraction) response in rings with endothelium under resting tension. Hypoxia produced a further contraction in rings precontracted with KCl or $PGF_{2{\alpha}}$, and following reoxygenation caused only sustained relaxation. Removal of the endothelium and pretreatment with nimodipine or indomethacin markedly attenuated the hypoxia- and reoxygenation-induced contractions. The KCl-induced contraction was not affected in hypoxic state, but contractions induced by $PGF_{2{\alpha}}$ or endothelin (ET) were inhibited in the hypoxia, the latter being more sensitive to the hypoxia. Upon reoxygenation, the attenuated contraction rapidly recovered to the original tension. Both hypoxia and reoxygenation significantly increased cyclic GMP content in the intact preparations, but not in the endothelium-removed ones. Acetylcholine (ACh) produced concentration-dependent relaxations in the intact endothelial rings precontracted with $PGF_{2{\alpha}}$ or endothelin, and the ACh-induced relaxation was inhibited by removal of endothelium and by hypoxia. ACh also increased cyclic GMP content in tissues pretreated with $PGF_{2{\alpha}}$ and the increase of cyclic GMP was abolished in hypoxic state. These results suggest that hypoxia- and reoxygenation-induced contractions are dependent on endothelium and extracellular calcium, and related to the release of prostaglandin-like substance(s).

• The Korean Journal of Pain
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• v.27 no.3
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• pp.229-238
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• 2014

Background: A toxic dose of bupivacaine produces vasodilation in isolated aortas. The goal of this in vitro study was to investigate the cellular mechanism associated with bupivacaine-induced vasodilation in isolated endothelium-denuded rat aortas precontracted with phenylephrine. Methods: Isolated endothelium-denuded rat aortas were suspended for isometric tension recordings. The effects of nifedipine, verapamil, iberiotoxin, 4-aminopyridine, barium chloride, and glibenclamide on bupivacaine concentration-response curves were assessed in endothelium-denuded aortas precontracted with phenylephrine. The effect of phenylephrine and KCl used for precontraction on bupivacaine-induced concentration-response curves was assessed. The effects of verapamil on phenylephrine concentration-response curves were assessed. The effects of bupivacaine on the intracellular calcium concentration ($[Ca^{2+}]_i$) and tension in aortas precontracted with phenylephrine were measured simultaneously with the acetoxymethyl ester of a fura-2-loaded aortic strip. Results: Pretreatment with potassium channel inhibitors had no effect on bupivacaine-induced relaxation in the endothelium-denuded aortas precontracted with phenylephrine, whereas verapamil or nifedipine attenuated bupivacaine-induced relaxation. The magnitude of the bupivacaine-induced relaxation was enhanced in the 100mM KCl-induced precontracted aortas compared with the phenylephrine-induced precontracted aortas. Verapamil attenuated the phenylephrine-induced contraction. The magnitude of the bupivacaine-induced relaxation was higher than that of the bupivacaine-induced $[Ca^{2+}]_i$ decrease in the aortas precontracted with phenylephrine. Conclusions: Taken together, these results suggest that toxic-dose bupivacaine-induced vasodilation appears to be mediated by decreased calcium sensitization in endothelium-denuded aortas precontracted with phenylephrine. In addition, potassium channel inhibitors had no effect on bupivacaine-induced relaxation. Toxic-dose bupivacaine-induced vasodilation may be partially associated with the inhibitory effect of voltage-operated calcium channels.

• 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).

• IMMUNE NETWORK
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• v.9 no.5
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• pp.153-157
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• 2009

The leukocyte adhesion to endothelium is pivotal in leukocyte recruitment which takes place during inflammatory, autoimmune and infectious conditions. The interaction between leukocytes and endothelium requires an array of adhesion molecules expressed on leukocytes and endothelial cells, thereby promoting leukocyte recruitment into sites of inflammation and tissue injury. Intervention with the adhesion molecules provides a platform for development of anti-inflammatory therapeutics. This review will focus on developmental endothelial locus-1 (Del-1), an endogenous inhibitor of leukocyte adhesion.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.11a
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• pp.36-38
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• 1993

내피세포 (endothelial cells, EC)는 amine, peptide, 단백, arachidonic acid 및 그 대사물 등의 여러 화학물질에 의하여 내피세포 의전성 이완물질 endothelium-derived relaxing factor, EDRF)을 유리할 뿐만 아니라 맥압(脈壓)과 같은 물리적 변동에 의하여서도 EDRF가 유리된다. EDRF는 처음에 Furchgott와 Zawadzki (1980)에 의하여 보고되었고, EDRF의 실질적인 성분이 무엇인가에 대하여는 그동안 많이 검토되어 왔다(Marshall 와 Kontos, Hong 등, 1990).Ignarro 등 (1987)과 Palmer등 (1987)은 EDRF에 의한 생물학적 반응이 NO (nitric oxide)와 유사하거나 같은 물질이라고 보고하였고,Furchgott 등 (1986)과 Ignarro등 (1988)도 EDRF가 NO와 유사하거나 같은 물질일 것이라고 단정하였다.