| Colforsin-induced vasodilation in chronic hypoxic pulmonary hypertension in rats. | |
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MedLine Citation:
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PMID: 20300779 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: Colforsin, a water-soluble forskolin derivative, directly activates adenylate cyclase and thereby increases the 3',5'-cyclic adenosine monophosphate (cAMP) level in vascular smooth muscle cells. In this study, we investigated the vasodilatory action of colforsin on structurally remodeled pulmonary arteries from rats with pulmonary hypertension (PH). METHODS: A total of 32 rats were subjected to hypobaric hypoxia (380 mmHg, 10% oxygen) for 10 days to induce chronic hypoxic PH, while 39 rats were kept in room air. Changes in isometric force were recorded in endothelium-intact (+E) and -denuded (-E) pulmonary arteries from the PH and control (non-PH) rats. RESULTS: Colforsin-induced vasodilation was impaired in both +E and -E arteries from PH rats compared with their respective controls. Endothelial removal did not influence colforsin-induced vasodilation in the arteries from control rats, but attenuated it in arteries from PH rats. The inhibition of nitric oxide (NO) synthase did not influence colforsin-induced vasodilation in +E arteries from controls, but attenuated it in +E arteries from PH rats, shifting its concentration-response curve closer to that of -E arteries from PH rats. Vasodilation induced by 8-bromo-cAMP (a cell-permeable cAMP analog) was also impaired in -E arteries from PH rats, but not in +E arteries from PH rats, compared with their respective controls. CONCLUSIONS: cAMP-mediated vasodilatory responses without beta-adrenergic receptor activation are impaired in structurally remodeled pulmonary arteries from PH rats. In these arteries, endothelial cells presumably play a compensatory role against the impaired cAMP-mediated vasodilatory response by releasing NO (and thereby attenuating the impairment). The results suggest that colforsin could be effective in the treatment of PH. |
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Authors:
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Ayumu Yokochi; Hiroo Itoh; Junko Maruyama; Erquan Zhang; Baohua Jiang; Yoshihide Mitani; Chikuma Hamada; Kazuo Maruyama |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-19 |
Journal Detail:
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Title: Journal of anesthesia Volume: 24 ISSN: 1438-8359 ISO Abbreviation: J Anesth Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-14 Completed Date: 2010-09-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8905667 Medline TA: J Anesth Country: Japan |
Other Details:
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Languages: eng Pagination: 432-40 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology and Critical Care Medicine, Faculty of Medicine, University of Mie, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. yokoti@clin.medic.mie-u.ac.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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8-Bromo Cyclic Adenosine Monophosphate
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pharmacology Animals Anoxia / drug therapy Chronic Disease Dinoprost / pharmacology Drug Synergism Fluorescent Dyes Forskolin / analogs & derivatives*, therapeutic use Fura-2 Hypertension, Pulmonary / drug therapy*, physiopathology Hypertrophy, Right Ventricular / drug therapy, physiopathology Isometric Contraction / drug effects Male Muscle Contraction / drug effects Potassium Chloride / pharmacology Pulmonary Artery / drug effects Rats Rats, Wistar Vasodilation / drug effects Vasodilator Agents / therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/Fluorescent Dyes; 0/Vasodilator Agents; 138605-00-2/colforsin; 23583-48-4/8-Bromo Cyclic Adenosine Monophosphate; 551-11-1/Dinoprost; 66428-89-5/Forskolin; 7447-40-7/Potassium Chloride; 96314-98-6/Fura-2 |
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