Chest ACCP Member Benefits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (13)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Miyata, M.
Right arrow Articles by Kasukawa, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Miyata, M.
Right arrow Articles by Kasukawa, R.
(Chest. 2001;119:554-561.)
© 2001 American College of Chest Physicians

Effect of a Serotonin Receptor Antagonist on Interleukin-6-Induced Pulmonary Hypertension in Rats*

Masayuki Miyata, MD, PhD; Masayuki Ito, MD, PhD; Tomomi Sasajima, MD; Hiromasa Ohira, MD, PhD and Reiji Kasukawa, MD, PhD

* From the Department of Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima, Japan.

Correspondence to: Masayuki Miyata, MD, Department of Internal Medicine II, Fukushima Medical University School of Medicine, 1 st. Hikarigaoka, Fukushima-City, Fukushima, Japan; e-mail: metm{at}msg.biglobe.ne.jp

Study objectives: To determine the significance of serotonin in the pathogenesis of interleukin (IL) 6-induced pulmonary hypertension (IL-6-PH) in rats, the plasma serotonin concentrations, and the effects of a specific antagonist of the serotonin (5-hydroxytryptamine [5-HT]) receptor, 1-[o-(m-methoxyphenyl)ethyl]phenoxy]-3-(dimethylamino)-2-propyl hydrogen succinate hydrochloride (MCI) on the degree of pulmonary hypertension (PH) were investigated in MCI-treated IL-6-PH (IL-6-MCI-PH) rats.

Measurements: The thickness of the media of small pulmonary arteries and the ratio of the weight of the right ventricle free wall (RV) to that of the left ventricle with the septum (LV + S) were measured as indexes of the degree of PH. Serotonin concentrations in plasma and in supernatants of cultured vascular smooth muscle cells (VSMCs) stimulated by IL-6 were measured by high-performance liquid chromatography. The amplification of DNA encoding the 5-HT receptor in the lung specimen and VSMCs was performed by polymerase chain reaction.

Results: The degree of PH, as determined by the medial thickness of small pulmonary arteries, was significantly increased in IL-6-PH rats as compared with normal control rats (p < 0.05), and that in IL-6-MCI-PH rats was not significantly different from that in normal control rats. The RV/LV + S weight ratio in the IL-6-PH rats was significantly higher than that in normal control rats (p < 0.01). The RV/LV + S weight ratio in IL-6-MCI-PH rats was significantly lower than that in IL-6-PH rats (p < 0.01) and was not significantly different from that in normal control rats. The serotonin concentration was significantly higher in IL-6-PH rats than in normal control rats (p < 0.02), and the serotonin concentration in IL-6-MCI-PH rats was not significantly different from that in the normal control rats. The expression levels of the 5-HT receptor messenger RNA in the lung tissue tended to increase in IL-6-PH rats but was suppressed in IL-6-MCI-PH rats. IL-6 significantly increased the amount of serotonin released from VSMCs (p < 0.02). The expression of the 5-HT receptor messenger RNA was observed with IL-6 stimulation as was observed with serotonin stimulation in VSMCs.

Conclusions: Serotonin receptor antagonists could be considered as potentially useful agents for the treatment of chronic thromboembolic PH, as well as for that of primary PH and PH associated with collagen vascular diseases.

Key Words: 5-hydroxytryptamine • interleukin 6 • MCI-9042 • pulmonary hypertension • serotonin • serotonin receptor • serotonin receptor antagonist • thromboembolic pulmonary hypertension






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the American College of Chest Physicians.