Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia.
Chronic intermittent hypoxia (IH) induces activation of the sympathoadrenal system, which plays a pivotal role in attenuating hypoxic pulmonary vasoconstriction (HPV) via central β1-adrenergic receptors (AR) (brain) and peripheral β2AR (pulmonary arteries). Prolonged hypercatecholemia has been shown...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4489089?pdf=render |
| _version_ | 1828299123905789952 |
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| author | Hisashi Nagai Ichiro Kuwahira Daryl O Schwenke Hirotsugu Tsuchimochi Akina Nara Sayoko Ogura Takashi Sonobe Tadakatsu Inagaki Yutaka Fujii Rutsuko Yamaguchi Lisa Wingenfeld Keiji Umetani Tatsuo Shimosawa Ken-Ichi Yoshida Koichi Uemura James T Pearson Mikiyasu Shirai |
| author_facet | Hisashi Nagai Ichiro Kuwahira Daryl O Schwenke Hirotsugu Tsuchimochi Akina Nara Sayoko Ogura Takashi Sonobe Tadakatsu Inagaki Yutaka Fujii Rutsuko Yamaguchi Lisa Wingenfeld Keiji Umetani Tatsuo Shimosawa Ken-Ichi Yoshida Koichi Uemura James T Pearson Mikiyasu Shirai |
| author_sort | Hisashi Nagai |
| collection | DOAJ |
| description | Chronic intermittent hypoxia (IH) induces activation of the sympathoadrenal system, which plays a pivotal role in attenuating hypoxic pulmonary vasoconstriction (HPV) via central β1-adrenergic receptors (AR) (brain) and peripheral β2AR (pulmonary arteries). Prolonged hypercatecholemia has been shown to upregulate β3AR. However, the relationship between IH and β3AR in the modification of HPV is unknown. It has been observed that chronic stimulation of β3AR upregulates inducible nitric oxide synthase (iNOS) in cardiomyocytes and that IH exposure causes expression of iNOS in RAW264.7 macrophages. iNOS has been shown to have the ability to dilate pulmonary vessels. Hence, we hypothesized that chronic IH activates β3AR/iNOS signaling in pulmonary macrophages, leading to the promotion of NO secretion and attenuated HPV. Sprague-Dawley rats were exposed to IH (3-min periods of 4-21% O2) for 8 h/d for 6 weeks. The urinary catecholamine concentrations of IH rats were high compared with those of controls, indicating activation of the sympathoadrenal system following chronic IH. Interestingly, chronic IH induced the migration of circulating monocytes into the lungs and the predominant increase in the number of pro-inflammatory pulmonary macrophages. In these macrophages, both β3AR and iNOS were upregulated and stimulation of the β3AR/iNOS pathway in vitro caused them to promote NO secretion. Furthermore, in vivo synchrotron radiation microangiography showed that HPV was significantly attenuated in IH rats and the attenuated HPV was fully restored by blockade of β3AR/iNOS pathway or depletion of pulmonary macrophages. These results suggest that circulating monocyte-derived pulmonary macrophages attenuate HPV via activation of β3AR/iNOS signaling in chronic IH. |
| first_indexed | 2024-04-13T12:51:11Z |
| format | Article |
| id | doaj.art-5ddc57058b974a23a7dcdcd2087f9692 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T12:51:11Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-5ddc57058b974a23a7dcdcd2087f96922022-12-22T02:46:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e013192310.1371/journal.pone.0131923Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia.Hisashi NagaiIchiro KuwahiraDaryl O SchwenkeHirotsugu TsuchimochiAkina NaraSayoko OguraTakashi SonobeTadakatsu InagakiYutaka FujiiRutsuko YamaguchiLisa WingenfeldKeiji UmetaniTatsuo ShimosawaKen-Ichi YoshidaKoichi UemuraJames T PearsonMikiyasu ShiraiChronic intermittent hypoxia (IH) induces activation of the sympathoadrenal system, which plays a pivotal role in attenuating hypoxic pulmonary vasoconstriction (HPV) via central β1-adrenergic receptors (AR) (brain) and peripheral β2AR (pulmonary arteries). Prolonged hypercatecholemia has been shown to upregulate β3AR. However, the relationship between IH and β3AR in the modification of HPV is unknown. It has been observed that chronic stimulation of β3AR upregulates inducible nitric oxide synthase (iNOS) in cardiomyocytes and that IH exposure causes expression of iNOS in RAW264.7 macrophages. iNOS has been shown to have the ability to dilate pulmonary vessels. Hence, we hypothesized that chronic IH activates β3AR/iNOS signaling in pulmonary macrophages, leading to the promotion of NO secretion and attenuated HPV. Sprague-Dawley rats were exposed to IH (3-min periods of 4-21% O2) for 8 h/d for 6 weeks. The urinary catecholamine concentrations of IH rats were high compared with those of controls, indicating activation of the sympathoadrenal system following chronic IH. Interestingly, chronic IH induced the migration of circulating monocytes into the lungs and the predominant increase in the number of pro-inflammatory pulmonary macrophages. In these macrophages, both β3AR and iNOS were upregulated and stimulation of the β3AR/iNOS pathway in vitro caused them to promote NO secretion. Furthermore, in vivo synchrotron radiation microangiography showed that HPV was significantly attenuated in IH rats and the attenuated HPV was fully restored by blockade of β3AR/iNOS pathway or depletion of pulmonary macrophages. These results suggest that circulating monocyte-derived pulmonary macrophages attenuate HPV via activation of β3AR/iNOS signaling in chronic IH.http://europepmc.org/articles/PMC4489089?pdf=render |
| spellingShingle | Hisashi Nagai Ichiro Kuwahira Daryl O Schwenke Hirotsugu Tsuchimochi Akina Nara Sayoko Ogura Takashi Sonobe Tadakatsu Inagaki Yutaka Fujii Rutsuko Yamaguchi Lisa Wingenfeld Keiji Umetani Tatsuo Shimosawa Ken-Ichi Yoshida Koichi Uemura James T Pearson Mikiyasu Shirai Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia. PLoS ONE |
| title | Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia. |
| title_full | Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia. |
| title_fullStr | Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia. |
| title_full_unstemmed | Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia. |
| title_short | Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via β3AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia. |
| title_sort | pulmonary macrophages attenuate hypoxic pulmonary vasoconstriction via β3ar inos pathway in rats exposed to chronic intermittent hypoxia |
| url | http://europepmc.org/articles/PMC4489089?pdf=render |
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