• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.463-468
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• 2013

Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated $K^+$ channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane $A_2$ ($TXA_2$) and hypoxia-activated nonselective cation channel ($I_{NSC}$) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d-H). Specifically, the associated electrophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d-H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d-H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d-H and control. In contrast, hypoxia and $TXA_2$-activated $I_{NSC}$ was not observed in PASMCs of 2d-H. From above results, it is suggested that the decreased $I_{NSC}$ might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.

• Tuberculosis and Respiratory Diseases
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• v.39 no.4
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• pp.299-303
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• 1992

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.59-64
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• 2012

Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response for preventing mismatching between ventilation and perfusion in lungs. The HPV of isolated pulmonary arteries (HPV-PA) usually require a partial pretone by thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV-lung) can be triggered without pretone conditioning, we suspected that a putative tissue factor might be responsible for the pretone of HPV. Here we investigated whether HPV can be also observed in precision-cut lung slices (PCLS) from rats. The HPV in PCLS also required partial contraction by U46619. In addition, $K^+$ channel blockers (4AP and TEA) required U46619-pretone to induce significant contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible contraction in response to the $K^+$ channel blockers without pretone conditioning. Also, the airways showed no hypoxic constriction but a relaxation under the partial pretone by U46619. The airways in PCLS showed reliable, concentration-dependent contraction by metacholine ($EC_{50}$, ~210 nM). In summary, the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholineinduced constriction of bronchioles suggested that the PLCS might be also useful for studying airway physiology in situ.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.321-328
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• 1999

Pulmonary blood vessels with diameters of $200{\sim}400\;{\mu}m$ produce considerably more force in response to vasoconstrictor drugs than those which are either smaller or larger. We have therefore investigated whether or not hypoxic pulmonary vasoconstriction (HPV) is more powerful in vessels of these diameters. We have also looked at the possibility that vessels from different regions of the lung respond differently. To do this we have grouped vessels according to their location within the lung as well as by size. We used a small vessel myograph (Cambustion AM10, Cambridge, UK) to study 208 preconstricted $(1\;{\mu}M\;PGF_{2{\alpha}})$ small pulmonary arteries $(300{\sim}800\;{\mu}m$ diameter when stretched to a tension equivalent to 25 mmHg transmural pressure) from 39 rats anaesthetized with 2% inspired halothane. A biphasic contraction was observed in response to hypoxia (ca. 25 mmHg $Po_2).$ The magnitudes of both the first, transient, phase (PT, peak tension) and of the second, sustained, phase (SST, steady state tension) were measured. The latter was measured 40 min after the start of hypoxia. The first phase was most pronounced in vessels with an average diameter of 423 ${\mu}m$ while the second phase was most pronounced in larger vessels (mean diameter 505 ${\mu}m).$ These maximal responses were all seen in vessels somewhat larger than reported by others. The responses of smaller vessels $(400{\sim}500\;{\mu}m)$ did not depend upon their location within the lung, but those of larger vessels $(600{\sim}700\;{\mu}m)$ showed regional differences. Those from the right lobe and those from the base of the lung gave the largest responses. It was especially noticeable that large vessels (631 ${\mu}m$ diameter) from the base of the right lung gave the biggest responses. Thus HPV seems to occur not in a uniform manner, dependent solely to the size of vessels, but it also depends to some degree on the region of the lung from which vessels have been taken. Furthermore, our results suggest that larger vessels, as well as smaller ones, may contribute significantly to HPV.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.641-647
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• 2016

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats. Using hematoxylin and eosin staining, we confirmed vascular remodeling (i.e., medial thickening of PA) and right ventricle hypertrophy in PAH-MCT rats. The basal pulmonary arterial pressure (PAP) and PAP increase by a raised flow rate (40 mL/min) were higher in the PAH-MCT than in the control rats. In addition, both high $K^+$ (40 mM KCl)- and angiotensin II-induced PAP increases were higher in the PAH-MCT than in the control rats. Surprisingly, application of a nitric oxide synthase inhibitor, L-$N^G$-Nitroarginine methyl ester (L-NAME), induced a marked PAP increase in the PAH-MCT rats, suggesting that endothelial functions were recovered in the three-week PAH-MCT rats. In addition, the medial thickening of the PA was similar to that in chronic hypoxia-induced PAH (PAH-CH) rats. However, the HPV response (i.e., PAP increased by acute hypoxia) was not affected in the MCT rats, whereas HPV disappeared in the PAH-CH rats. These results showed that vascular contractility and HPV remain robust in the MCT-induced PAH rat model with vascular remodeling.

• The Korean Journal of Nuclear Medicine
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• v.35 no.4
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• pp.288-290
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• 2001

A 61 year-old woman underwent perfusion and inhalation lung scan for the evaluation of pulmonary thromboembolism. Tc-99m MAA perfusion lung scan showed multiple round hot spots in both lung fields. Tc-99m DTPA aerosol inhalation lung scan and chest radiography taken at the same time showed normal findings (Fig. 1, 2). A repeated perfusion lung scan taken 24 hours later demonstrated no abnormalities (Fig. 3). Hot spots on perfusion lung scan can be caused by microsphere clumping due to faulty injection technique or by radioactive embolization from upper extremity thrombophlebitis after injection. Focal hot spots can signify zones of atelectasis, where the hot spots probably represent a failure of hypoxic vasoconstriction. Artifactual hot spots due to microsphere clumping usually appear to be round and in peripheral location, and the lesions due to a loss of hypoxic vasoconstriction usually appear to be hot uptakes having linear $borders^{1-3)}$. Although these artifactual hot spots have been well-known, we rarely encounter them. This report presents a case with artifactual hot spots due to microsphere clumping on Tc-99m MAA perfusion lung scan.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.231-238
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• 1994

Backgroud: Since the demonstration of the fact that vascular relaxation by acetylcholine(Ach) results from the release of relaxing factor from the endothelium, the identity and physiology of this endothelium-derived relaxing factor(EDRF) has been the target for many researches. EDRF has been identified as nitric oxide(NO). With the recent evidences that EDRF is an important mediator of vascular tone, there have been increasing interests in defining the role of the EDRF as a potential mediator of hypoxic pulmonary vasoconstriction. But the role of EDRF in modulating the pulmonary circulation is not compeletely clarified. To investigate the endothelium-dependent pulmonary vasodilation and the role of EDRF during hypoxic pulmonary vasoconstriction, we studied the effects of $N^G$-monomethyl-L-arginine(L-NMMA) and L-arginine on the precontracted pulmonary arterial rings of the rat in normoxia and hypoxia. Mothods: The pulmonary arteries of male Sprague Dawley(300~350g) were dissected free of surrounding tissue, and cut into rings. Rings were mounted over fine rigid wires, in organ chambers filled with 20ml of Krebs solution bubbled with 95 percent oxygen and 5 percent carbon dioxide and maintained at $37^{\circ}C$. Changes in isometric tension were recorded with a force transducer(FT.03 Grass, Quincy, USA) Results: 1) Precontraction of rat pulmonry artery with intact endothelium by phenylephrine(PE, $10^{-6}M$) was relaxed completely by acetylcholine(Ach, $10^{-9}-10^{-5}M$) and sodium nitroprusside(SN, $10^{-9}-10^{-5}M$), but relaxing response by Ach in rat pulmonary artery with denuded endothelium was significantly decreased. 2) L-NMMA($10^{-4}M$) pretreatment inhibited Ach($10^{-9}-10^{-5}M$)-induced relaxation, but L-NMMA ($10^{-4}M$) had no effect on relaxation induced by SN($10^{-9}-10^{-5}M$). 3) Pretreatment of the L-arginine($10^{-4}M$) significantly reversed the inhibition of the Ach ($10^{-9}-10^{-5}M$)-induced relaxation caused by L-NMMA($10^{-4}M$) 4) Pulmonary arterial contraction by PE($10^{-6}M$) was stronger in hypoxia than normoxia but relaxing response by Ach($10^{-9}-10^{-5}M$) was decreased, 5) With pretreatment of L-arginine($10^{-4}M$), pulmonary arterial relaxation by Ach($10^{-9}-10^{-5}M$) in hypoxia was reversed to the level of relaxation in normoxia. Conclusion: It is concluded that rat pulmonary arterial relaxation by Ach is dependent on the intact endothelium and is largely mediated by NO. Acute hypoxic pulmonary vasoconstriction is related to the suppression on NO formation in the vascular endothelium.