• Journal of Chest Surgery
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• v.42 no.5
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• pp.588-596
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• 2009

Background: To clarify the effect of hypoxia on vascular contractility, we tried to show whether hypoxia induced the release of endothelium-derived relaxing factor (EDRF) and the nature of the underlying mechanism for this release. Material and Method: Isometric contractions were observed in rabbit aorta, and the released EDRF from the rabbit aorta was bioassayed by using rabbit denuded carotid artery. The intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in the cultured rabbit aortic endothelial cells was recorded by a microfluorimeter with using Fura-2/AM. Hypoxia was evoked to the blood vessels or endothelial cells by eliminating the $O_2$ in the aerating gases in the external solution. Chemical hypoxia was evoked by applying deoxyglucose or $CN^-$. Result: Hypoxia relaxed the precontracted rabbit thoracic aorta that had its endothelium, and the magnitude of the relaxation was gradually increased by repetitive bouts of hypoxia. In contrast, hypoxia-induced relaxation was not evoked in the aorta that was denuded of endothelium. In a bioassay experiment, hypoxia released endothelium-derived relaxing factor (EDRF) and the release was inhibited by L-NAME or the $K^+$ channel blocker tetraethylammonium (TEA). In the cultured endothelial cells, hypoxia augmented the ATP-induced increase of the intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) and this increase was inhibited by TEA. Furthermore, chemical hypoxia also increased the $Ca^{2+}$ influx. Conclusion: From these results, it can be concluded that hypoxia might induce the release of NO from rabbit aortic endothelial cells by increasing $[[Ca^{2+}]_i$.

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

• Journal of Chest Surgery
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• v.32 no.4
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• pp.333-340
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• 1999

Background: Plasminogen activator inhibitor-1(PAI-1) is known as the primary physiological inhibitor of tissue-type plasminogen activator(t-PA) in the plasma, and is present within the atherosclerotic vessels. Increased plasma levels of PAI-1 are one of the major disturbances of the hemostatic system in patients with diabetes and/or hypertension, and may have multiple interrelations with the important risk factors in the development of atherosclerosis. This study was performed to determine whether altered gene expression of PAI-1 occurs within the arterial wall, and thereby potentially contributing to the increase of cardiovascular risks associated with diabetes and/or hypertension. Material and Method: The aortic vascular smooth muscle cells of the rat were exposed to 22 mM glucose, angiotensin II, and insulin increased PAI-1 mRNA expression with the use of Northern blotting were examined. Also examined were the effects of 22 mM glucose, angiotensin II and insulin on the growth of the rat's aortic smooth muscle cells by using MTT assay. Result: Twenty-two mM glucose treatment increased the PAI-1 mRNA expression in a time- and dose-dependent manner. Aniotensin II treatment synergistically increased the glucose-induced PAI-1 mRNA expression. In contrast, addition of insulin attenuated the increase of 22 mM glucose and angiotensin II induced PAI-1 mRNA expression. Furthermore, treatment of 22 mM glucose, angiotensin II and insulin resulted in a significant increase in cell numbers. This study demonstrated that 22 mM glucose and angiotensin II have a synergistic effect in stimulating the PAI-1 mRNA expression and in the cell growth of the rat's aortic smooth muscle cells. Conclusion: Elevation of glucose and angiotensin II may be important risk factors in impairing fibrinolysis and developing atherosclerosis in diabetic patients.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.45-52
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• 1991

The inhibitory effects of GS354 and GS389 on cytosolic $Ca^{2+}$ level ($[Ca^{2+}]_{1}$; measured with fura-2 fluorescence) and muscle tension in vascular smooth muscle of rat thoracic aorta were investigated. Both GS354 and GS389 inhibited the contractions induced by high $K^+$ or by norepinephrine. The vasodilator effect of GS354 was accompanied by a decrease in $[Ca^{2+}]_{1}$. The inhibitory effect on high $K^+-stimulated$ $[Ca^{2+}]_{1}$ was antagonized by a $Ca^{2+}$ channel activator, Bay K8644. However, the inhibitory effect on muscle tension was not antagonized by Bay K8644. These results suggest that GS354 inhibits $Ca^{2+}$ channels to decrease $[Ca^{2+}]_{1}$ and also decreases $Ca^{2+}$ sensitivity of contractile elements. The inhibitory effects of GS389 was accompanied by the increase in tissue fluorescence. This increment was not due to fura-2 fluorescence but to endogeneous pyridine nucleotides, suggesting that GS389 has an effect to inhibit mitochondrial function. Because of this interference, effects of GS389 on $[Ca^{2+}]_{1}$ was obscured. However, since sequential addition of Bay K8644 in the presence of GS389 further increased the fluorescence but not muscle tension, this compound seems to have the effects to inhibit $Ca^{2+}$ channels and to decrease $Ca^{2+}$ sensitivity of contractile elements.