Hoecherl, Klaus and Schmidt, Christoph and Kurt, Birguel and Bucher, Michael (2008) Activation of the PGI(2)/IP system contributes to the development of circulatory failure in a rat model of endotoxic shock. HYPERTENSION, 52 (2). pp. 330-335. ISSN 0194-911X,
Full text not available from this repository. (Request a copy)Abstract
Prostacyclin levels are increased in septic patients and several animal models of septic shock, and selective inhibition of cyclooxygenase-2 improved cardiovascular dysfunction in rats treated with lipopolysaccharide (LPS). Here, we examine the specific role of prostacyclin and of the receptor for prostacyclin (IP) in the development of LPS-induced circulatory failure. Intravenous injection of LPS ( 10 mg/kg) into male Sprague-Dawley rats caused a strong increase in plasma prostacyclin levels, which was paralleled by a decrease in blood pressure and an increase in heart rate. Moreover, LPS injection increased the mRNA expression of the IP receptor in the heart, aorta, lung, liver, adrenal glands, and kidneys. Cotreatment with the IP antagonist CAY-10441 ( 1, 10, 30, and 100 mg/kg) dose-dependently moderated the LPS-induced changes in mean arterial blood pressure, heart rate, cardiac output, and systemic vascular resistance. The development of cardiovascular failure was ameliorated by CAY-10441 in spite of the typical LPS-induced increases in plasma levels of cytokines and NO. In vitro, cytokines dose-and time-dependently induced IP expression in rat vascular smooth muscle cells. Incubation of cells with the stable IP agonist iloprost in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-mehylxanthine resulted in higher cAMP levels in cytokine-treated cells compared with untreated cells. Taken together, our data demonstrate a prominent role of the prostacyclin/IP system in the development of LPS-induced cardiovascular failure.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE-CELLS; PROSTACYCLIN SYNTHASE; ENDOTHELIAL-CELLS; CYCLOOXYGENASE INHIBITION; PROSTAGLANDIN I-2; SEPTIC SHOCK; RECEPTOR; SEPSIS; prostacyclin; LPS; CAY-10441; blood pressure; sepsis |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie Biology, Preclinical Medicine > Institut für Physiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 11:07 |
| Last Modified: | 26 Oct 2020 11:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30531 |
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