Blumberg, Friedrich C. and Lorenz, Cornelia and Wolf, Konrad and Sandner, Peter and Riegger, Guenter A. J. and Pfeifer, Michael (2002) Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary hypertension. CARDIOVASCULAR RESEARCH, 55 (1): PII S0008-. pp. 171-177. ISSN 0008-6363
Full text not available from this repository. (Request a copy)Abstract
Objective: The regulation of pulmonary prostacyclin synthesis is not completely understood. We tested the hypothesis that prostacyclin production is predominantly stimulated by hemodynamic factors, such as increased shear-stress, and is thus increased in rats with chronic hypoxic pulmonary hypertension. Methods: To this end, we determined pulmonary prostacyclin synthase (PGIS) gene expression, circulating levels of the stable prostacyclin metabolite 6-keto prostaglandin F-1alpha (6-keto-PGF(1alpha)), pulmonary endothelin (ET)-1 gene expression, and ET-1 plasma levels in rats exposed to 4 weeks of hypoxia (10% O-2) in the presence or absence of either the nitric oxide (NO) donor molsidomine (MD, 15 mg/kg/day) or the ET-A receptor antagonist LU135252 (LU, 50 mg/kg/day). Results: Right ventricular systolic pressure (RVSP), the cross-sectional medial vascular wall area of pulmonary arteries, and ET-I production increased significantly during hypoxia. PGIS mRNA levels increased 1.7-fold, and 6-keto-PGF(1alpha) plasma levels rose from 8.2+/-0.8 to 12.2+/-2.2 ng/ml during hypoxia (each P<0.05 vs. normoxic controls). MD and LU reduced RVSP and pulmonary vascular remodeling similarly (each P<0.05 vs. hypoxia), but only MD inhibited pulmonary ET-1 formation (P<0.05 vs. hypoxia). Nevertheless, both drugs attenuated the increase in PGIS gene expression and plasma 6-keto-PGF(1alpha) levels (each P<0.05 vs. hypoxia). Conclusion: Out- data suggest that prostacyclin production in hypertensive rat lungs is predominantly increased by hemodynamic factors while hypoxia, NO and ET-1 per are less important stimuli, and that this increase may serve as a compensatory mechanism to partially negate the hypoxia-induced elevation in pulmonary vascular tone. (C) 2002 Elsevier Science B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-EXPRESSION; ENDOTHELIN RECEPTOR; SYNTHASE; PROSTAGLANDIN; LUNGS; CELLS; CDNA; VASOCONSTRICTION; THROMBOXANE; ANTAGONIST; endothelial factors; endothelins; hypoxia/anoxia; prostaglandins; pulmonary circulation |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II Biology, Preclinical Medicine > Institut für Physiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Oct 2021 11:21 |
| Last Modified: | 18 Oct 2021 11:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/40103 |
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