Activation of soluble guanylyl cyclase by a factor other than nitric oxide or carbon monoxide contributes to the vascular hyporeactivity to vasoconstrictor agents in the aorta of rats treated with endotoxin

Chin Chen Wu, Csaba Szabó, Shiu Jen Chen, Christoph Thiemermann, John R. Vane

    Research output: Contribution to journalArticle

    51 Scopus citations

    Abstract

    We have examined the role of soluble guanylyl cyclase and possible mediators of its activation in the vascular hyporeactivity caused by bacterial endotoxin (lipopolysaccharide, LPS) ex vivo. Treatment of rats with E. coli LPS (10 mg/kg, i.v. for 3h) resulted in a significant reduction in the contractions elicited by norepinephrine (NE; 10−9 -10−6 M) in endothelium-denuded aortic rings ex vivo. Methylene blue or LY-83583, inhibitors of soluble guanylyl cyclase, completely restored contractions to NE, whereas the nitric oxide synthase (NOS) inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), caused only a partial restoration. Zinc protoporphyrin-IX, an inhibitor of heme oxygenase, did not enhance NE-induced contraction in rings from LPS-treated rats, indicating that the production of carbon monoxide (CO) does not contribute to this vascular hyporeactivity. Indomethacin, an inhibitor of cyclooxygenase, further suppressed the contractions in rings from LPS-treated rats. These results suggest that hyporesponsiveness to NE caused by LPS is due to the activation of soluble guanylyl cyclase, which is partially mediated by NO, but not by CO, Moreover, LPS may induce the production of another mediator(s) that activate soluble guanyyl cyclase in the vascular smooth muscle.

    Original languageEnglish (US)
    Pages (from-to)436-442
    Number of pages7
    JournalBiochemical and Biophysical Research Communications
    Volume201
    Issue number1
    DOIs
    StatePublished - May 30 1994

    ASJC Scopus subject areas

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

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